Disease spectrum classification

Abstract

Described herein are systems, media, and methods for assessing an individual by generating a classification or regression based on input data comprising metabolite information, protein information, nucleic acid information, non-molecular information, or any combination thereof.

Description

BACKGROUND

Personalized medicine has the potential to detect various possible diseases, disorders, or conditions that are personalized to the individual patient based on molecular profiling. However, many challenges remain in generating therapeutically useful diagnoses.

SUMMARY

Described herein are platforms, systems, media, and methods for assessing an individual for one or more diseases, disorders, or conditions. A machine learning algorithm can be used to provide the assessment based on personalized data derived from the individual. The personalized data can include metabolite data from a specimen or biological sample of the individual.

In one aspect, described herein is a system for assessing an individual, comprising: (a) a processor; (b) a non-transitory computer readable medium encoded with software comprising one or more machine learning algorithms together with instructions configured to cause the processor to: (i) receive data related to a specimen taken from the individual; and (ii) provide the data as input to the one or more machine learning algorithms, wherein the one or more machine learning algorithms use the data to generate a classification of the individual relative to a plurality of related classifications. In some instances, the one or more machine learning algorithms comprise an ensemble of machine learning algorithms. Sometimes, the ensemble comprises at least three machine learning algorithms. In certain cases, the ensemble of machine learning algorithms comprises a Generalized Linear algorithm, a Random Forests algorithm, a Partial Least Squares algorithm, and Extreme Gradient Boosting algorithm, a Support Vector Machines with Linear Basis Function Kernel algorithm, a Support Vector Machines with Radial Basis Function Kernel, and a Neural Networks algorithm. In some cases, each machine learning algorithm of the ensemble of machine learning algorithms produces an output that is averaged by the software. Sometimes, each machine learning algorithm of the ensemble of machine learning algorithms produces an output and wherein at least one output is an input for at least one of the machine learning algorithms. In certain instances, the at least one machine learning algorithm is trained using data relating to specimens from other individuals. Oftentimes, the specimen comprises a biological sample. In some cases, the specimen comprises at least one of a sputum sample, a urine sample, a blood sample, a cerebrospinal fluid sample, a stool sample, a hair sample, and a biopsy. The data often relates to a metabolite. In certain instances, the metabolite comprises at least one of oleamide, creatine, and 4-methyl-2-oxopentanoate. Sometimes, the instructions are further configured to cause the processor to receive a parameter related to the individual and wherein the one or more machine learning algorithms use the parameter together with the data to generate the classification of the individual relative to the plurality of related classifications. The parameter often comprises at least one of an age, a gender, a race, a weight, a BMI, a height, a waist size, a blood pressure, a heart rate, and a temperature. Sometimes, the classification comprises a disease. In various instances, the disease comprises at least one of multiple sclerosis, amyotrophic lateral sclerosis, systemic lupus erythematosus, fibromyalgia, and gastrointestinal reflux disease. In certain cases, the plurality of related classifications comprise a spectrum of severity of a single disease. Sometimes, the plurality of related classifications comprise a spectrum of prognoses of a single disease. In certain instances, the plurality of related classifications comprise a spectrum of related diseases. The spectrum of related diseases comprise a plurality of neurological diseases that share at least one common feature, in various cases.

In another aspect, disclosed herein is a computer implemented method for assessing an individual, comprising: (a) receiving data relating to a specimen taken from the individual; (b) providing the data as input to one or more machine learning algorithms; and (c) generating, using the one or more machine learning algorithms, a classification of the individual relative to a plurality of related classifications based on the data. In some instances, the one or more machine learning algorithms comprise an ensemble of machine learning algorithms. Sometimes, the ensemble comprises at least three machine learning algorithms. In certain cases, the ensemble of machine learning algorithms comprises a Generalized Linear algorithm, a Random Forests algorithm, a Partial Least Squares algorithm, and Extreme Gradient Boosting algorithm, a Support Vector Machines with Linear Basis Function Kernel algorithm, a Support Vector Machines with Radial Basis Function Kernel, and a Neural Networks algorithm. In some cases, each machine learning algorithm of the ensemble of machine learning algorithms produces an output that is averaged by the software. Sometimes, each machine learning algorithm of the ensemble of machine learning algorithms produces an output and wherein at least one output is an input for at least one of the machine learning algorithms. In certain instances, the at least one machine learning algorithm is trained using data relating to specimens from other individuals. Oftentimes, the specimen comprises a biological sample. In some cases, the specimen comprises at least one of a sputum sample, a urine sample, a blood sample, a cerebrospinal fluid sample, a stool sample, a hair sample, and a biopsy. The data often relates to a metabolite. In certain instances, the metabolite comprises at least one of oleamide, creatine, and 4-methyl-2-oxopentanoate. Sometimes, the instructions are further configured to cause the processor to receive a parameter related to the individual and wherein the one or more machine learning algorithms use the parameter together with the data to generate the classification of the individual relative to the plurality of related classifications. The parameter often comprises at least one of an age, a gender, a race, a weight, a BMI, a height, a waist size, a blood pressure, a heart rate, and a temperature. Sometimes, the classification comprises a disease. In various instances, the disease comprises at least one of multiple sclerosis, amyotrophic lateral sclerosis, systemic lupus erythematosus, fibromyalgia, and gastrointestinal reflux disease. In certain cases, the plurality of related classifications comprise a spectrum of severity of a single disease. Sometimes, the plurality of related classifications comprise a spectrum of prognoses of a single disease. In certain instances, the plurality of related classifications comprise a spectrum of related diseases. The spectrum of related diseases comprise a plurality of neurological diseases that share at least one common feature, in various cases.

In another aspect, disclosed herein is a system for assessing an individual, comprising: (a) a processor; (b) a non-transitory computer readable medium encoded with software comprising one or more machine learning algorithms together with instructions configured to cause the processor to: (i) receive data related to a specimen taken from the individual; and (ii) provide the data as input to the one or more machine learning algorithms, wherein the one or more machine learning algorithms use the data to generate an assessment of one or more traits of the individual. In some cases, the one or more machine learning algorithms comprise an ensemble of machine learning algorithms. Sometimes, the ensemble comprises at least three machine learning algorithms. In some aspects, the ensemble of machine learning algorithms comprises a Generalized Linear algorithm, a Random Forests algorithm, a Partial Least Squares algorithm, and Extreme Gradient Boosting algorithm, a Support Vector Machines with Linear Basis Function Kernel algorithm, a Support Vector Machines with Radial Basis Function Kernel, and a Neural Networks algorithm. In certain instances, each machine learning algorithm of the ensemble of machine learning algorithms produces an output that is averaged by the software. In various aspects, each machine learning algorithm of the ensemble of machine learning algorithms produces an output and wherein at least one output is an input for at least one of the machine learning algorithms. In certain cases, at least one machine learning algorithm is trained using data relating to specimens from other individuals. Sometimes, the specimen comprises a biological sample. In some instances, the specimen comprises at least one of a sputum sample, a urine sample, a blood sample, a cerebrospinal fluid sample, a stool sample, a hair sample, and a biopsy. In certain aspects, the data relates to a metabolite, a protein, a nucleic acid, or any combination thereof. In various cases, the metabolite comprises at least one of oleamide, creatine, and 4-methyl-2-oxopentanoate. Sometimes, the instructions are further configured to cause the processor to receive a parameter related to the individual and wherein the one or more machine learning algorithms use the parameter together with the data to generate the assessment of the individual. In some cases, the parameter comprises at least one of an age, a gender, a race, a weight, a BMI, a height, a waist size, a blood pressure, a heart rate, and a temperature. In certain aspects, the assessment comprises at least one trait selected from a category that is personal characteristics, general health, mental health, health behaviors, interventions, organ systems, environmental, or conditions. In some instances, the one or more traits comprises at least one of sex, age, BMI, race, ethnicity, personality, traits, family history, current, conditions, acute infection, allergies, perceived health, circadian cycle, menstrual cycle, genetic predisposition, thrive, cognition, energy, depression, anxiety, stress, coping ability, feels good or bad, fitness, substances, sleep, diet, sun exposure, sex drive, vaccines, treatment, procedures, supplement, circulatory, dental, digestive, endocrine, lymph or immune system, metabolism, musculoskeletal system, nervous system, renal system, reproductive system, respiratory system, skin, life events including trauma, living environment, work environment, chemical, exposures, social functioning, diagnostic history, disease severity, symptoms and signs, potential, complications, and, comorbidities, monitoring labs and tests, or treatment.

In another aspect, disclosed herein is a computer implemented method for assessing an individual, comprising: (a) receiving data relating to a specimen taken from the individual; (b) providing the data as input to one or more machine learning algorithms; and (c) generating, using the one or more machine learning algorithms, an assessment of one or more traits of the individual. In some cases, the one or more machine learning algorithms comprise an ensemble of machine learning algorithms. Sometimes, the ensemble comprises at least three machine learning algorithms. In some aspects, the ensemble of machine learning algorithms comprises a Generalized Linear algorithm, a Random Forests algorithm, a Partial Least Squares algorithm, and Extreme Gradient Boosting algorithm, a Support Vector Machines with Linear Basis Function Kernel algorithm, a Support Vector Machines with Radial Basis Function Kernel, and a Neural Networks algorithm. In certain instances, each machine learning algorithm of the ensemble of machine learning algorithms produces an output that is averaged by the software. In various aspects, each machine learning algorithm of the ensemble of machine learning algorithms produces an output and wherein at least one output is an input for at least one of the machine learning algorithms. In certain cases, at least one machine learning algorithm is trained using data relating to specimens from other individuals. Sometimes, the specimen comprises a biological sample. In some instances, the specimen comprises at least one of a sputum sample, a urine sample, a blood sample, a cerebrospinal fluid sample, a stool sample, a hair sample, and a biopsy. In certain aspects, the data relates to a metabolite, a protein, a nucleic acid, or any combination thereof. In various cases, the metabolite comprises at least one of oleamide, creatine, and 4-methyl-2-oxopentanoate. Sometimes, the method further comprises receiving a parameter related to the individual and wherein the one or more machine learning algorithms use the parameter together with the data to generate the assessment of the individual. In some cases, the parameter comprises at least one of an age, a gender, a race, a weight, a BMI, a height, a waist size, a blood pressure, a heart rate, and a temperature. In certain aspects, the assessment comprises at least one trait selected from a category that is personal characteristics, general health, mental health, health behaviors, interventions, organ systems, environmental, or conditions. In some instances, the one or more traits comprises at least one of sex, age, BMI, race, ethnicity, personality, traits, family history, current, conditions, acute infection, allergies, perceived health, circadian cycle, menstrual cycle, genetic predisposition, thrive, cognition, energy, depression, anxiety, stress, coping ability, feels good or bad, fitness, substances, sleep, diet, sun exposure, sex drive, vaccines, treatment, procedures, supplement, circulatory, dental, digestive, endocrine, lymph or immune system, metabolism, musculoskeletal system, nervous system, renal system, reproductive system, respiratory system, skin, life events including trauma, living environment, work environment, chemical, exposures, social functioning, diagnostic history, disease severity, symptoms and signs, potential, complications, and, comorbidities, monitoring labs and tests, or treatment.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention are set forth with particularity in the appended claims. The file of this patent contains at least one drawing/photograph executed in color. Copies of this patent with color drawing(s)/photograph(s) will be provided by the Office upon request and payment of the necessary fee. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:

FIG. 1 shows a list of conditions and the corresponding number of participants having metabolite data that are reported to have each condition. Those conditions that have been evaluated according to the methods described herein have at least 35 participants and are bracketed by the box;

FIG. 2A, FIG. 2B, and FIG. 2C show heat maps of the AUC performance of 8 different machine learning algorithms or classifiers including the Ensemble classifier that are trained and tested using 3 different subpopulations of the participant data. The classifiers are listed on the X-axis, and the various diseases, disorders, or conditions are listed on the Y-axis. The classifiers were trained and tested using participant metabolite data.

FIG. 3A, FIG. 3B, and FIG. 3C show the AUC curves of the Ensemble classifier trained and tested using for 3 different subpopulations of participant data for multiple sclerosis. FIG. 3D shows a model summary that averages the individual Ensembles from FIGS. 3A-3C.

FIG. 4A, FIG. 4B, and FIG. 4C show the AUC curves of the Ensemble classifier trained and tested using for 3 different subpopulations of participant data for amyotrophic lateral sclerosis. FIG. 4D shows a model summary that averages the individual Ensembles from FIGS. 4A-4C.

FIG. 5A, FIG. 5B, FIG. 5C, FIG. 5D, FIG. 5E, FIG. 5F, FIG. 5G, FIG. 5H, FIG. 5I, and FIG. 5J show some high performing Ensemble classifiers based on disease, disorder, or condition. FIG. 5A shows the AUC curve for amyotrophic lateral sclerosis. FIG. 5B shows the AUC curve for multiple sclerosis. FIG. 5C shows the AUC curve for bipolar disorder. FIG. 5D shows the AUC curve for systemic lupus erythematosus. FIG. 5E shows the AUC curve for fibromyalgia. FIG. 5F shows the AUC curve for generalized anxiety disorder. FIG. 5G shows the AUC curve for osteoarthritis. FIG. 5H shows the AUC curve for gastroesophageal reflux disease. FIG. 5I shows the AUC curve for high blood pressure. FIG. 5J shows the AUC curve for major depressive disorder.

FIG. 6A shows a diagram of disease spectrum metabolite scores showing a healthy range (green/non-disease) overlaid with a participant score (red). FIG. 6B shows a diagram of disease spectrum metabolite scores for an individual on a diet. The disease spectrum metabolite scores can be monitored over time (e.g., from repeated metabolite sampling) to determine progression of a disease, disorder, or condition as well as response to various therapeutic interventions such as, for example, diet as shown in FIG. 6B.

FIG. 7A shows the model score for diet participants with a threshold of 0.85 for positive classification of osteoarthritis. FIG. 7B shows the model scores for diet participants with a threshold of 0.91 for positive classification of high blood pressure.

FIG. 8A, FIG. 8B, FIG. 8C, FIG. 8D, FIG. 8E, FIG. 8F, and FIG. 8G show diagrams of before (left) and after (right) disease spectrum metabolite scores for diet participants.

FIG. 9A shows a diagram of disease spectrum scores for a participant who has multiple sclerosis and amyotrophic lateral sclerosis. FIG. 9B shows the model scores for diet participants with a threshold of 0.46 for positive classification of multiple sclerosis.

FIG. 10A shows a diagram of disease spectrum scores for a participant who has amyotrophic lateral sclerosis. FIG. 10B shows the model scores for diet participants with a threshold of 0.56 for positive classification of amyotrophic lateral sclerosis.

FIGS. 11A-11B shows training and testing statistics for multiple sclerosis using 7 different machine learning models based on 89 MS positive cases and 292 MS negative cases. The results are based on 100 re-samplings of 5-fold cross-validation repeated 20 times. FIG. 11A shows the 0.95 confidence interval for ROC for 7 different machine learning algorithms or classifiers. FIG. 11B shows the 0.95 confidence interval for sensitivity for 7 different machine learning algorithms or classifiers. FIG. 11C shows the 0.95 confidence interval for specificity for 7 different machine learning algorithms or classifiers.

FIG. 12 shows AUC curves for the 7 different machine learning algorithms or classifiers and the Ensemble classifier with respect to multiple sclerosis (22 MS positive cases; 89 MS negative cases): FIG. 12A generalized linear model; FIG. 12B partial least squares; FIG. 12C support vector machine; FIG. 12D radial kernel SVM; FIG. 12E random forest; FIG. 12F extreme gradient boosting; FIG. 12G neural network; FIG. 12H Ensemble.

FIG. 13A shows an AUC curve for an Ensemble classifier for classifying multiple sclerosis with an AUC of 0.891. The model correctly called 47 of 53 MS positive cases (89%) with 6 false negatives (11%) and correctly called 141 of 179 MS negative cases (79%) with 38 false positives (21%). Of the 38 false positives, 28 were ALS positive, indicating that using a combination of MS and ALS classifiers would enhance performance.

FIG. 13B shows the same AUC curve as FIG. 13A but using an alternative threshold that maximizes specificity (see dotted line). Using this alternative threshold, the model correctly called 39 of 53 MS positive cases (74%) with 14 false negatives (26%) and correctly called 158 of 179 MS negative cases (88%) with 21 false positives (12%). Of the 21 false positives, 17 were ALS positive.

FIG. 14 shows a list of 38 participants classified as false positives according to the model from FIG. 13. FIG. 14 shows various relevant parameters including the participant number, reported MS status, score, call (prediction according to FIG. 13A), optimal specificity (call/prediction according to FIG. 13B when optimizing specificity), participant condition, number, and ALS and MS status.

FIG. 15A shows a table with various features used in MS classifiers and corresponding pathway information. FIG. 15B shows the same feature list with corresponding feature importance based on the best performing models in CV.

FIG. 16 shows self-reported multiple sclerosis treatments.

FIG. 17A shows a table with various features used in MS classifiers and corresponding pathway information. FIG. 17B shows the same feature list with drugs and/or specific supplements identified for the various metabolites in the feature list.

FIG. 18A shows a map of the AUC performance of 8 different machine learning algorithms or classifiers including the Ensemble classifier when supplements are not excluded from the feature list. FIG. 18B shows an AUC curve for the MS Ensemble classifier for MS with an AUC of 0.866 with supplements. FIG. 18C shows a map of the AUC performance of 8 different machine learning algorithms or classifiers including the Ensemble classifier when supplements are excluded from the feature list. FIG. 18D shows an AUC curve for the MS Ensemble classifier for MS with an AUC of 0.845 without supplements.

FIGS. 19A-19B shows training and testing statistics for amyotrophic lateral sclerosis using 7 different machine learning models based on 84 ALS positive cases and 296 ALS negative cases. The results are based on 100 re-samplings of cross-validation. FIG. 19A shows the 0.95 confidence interval for ROC for 7 different machine learning algorithms or classifiers. FIG. 19B shows the 0.95 confidence interval for sensitivity for 7 different machine learning algorithms or classifiers. FIG. 19C shows the 0.95 confidence interval for specificity for 7 different machine learning algorithms or classifiers.

FIG. 20 shows AUC curves for the 7 different machine learning algorithms or classifiers and the Ensemble classifier with respect to amyotrophic lateral sclerosis (21 ALS positive cases; 91 ALS negative cases): FIG. 20A generalized linear model; FIG. 20B partial least squares; FIG. 20C support vector machine; FIG. 20D SVMR; FIG. 20E random forest; FIG. 20F extreme gradient boosting; FIG. 20G neural network; FIG. 20H Ensemble.

FIG. 21 shows an AUC curve for an ALS metabolite summary score model with an AUC of 0.908. The model correctly classifies 41 of 54 ALS positive cases (76%) with a false negative of 13 (24%). The model also correctly classifies 164 of 168 ALS negative cases (98%) with 4 false positives (92%). Of the 4 false positives, 2 were MS positive.

FIG. 22A shows a table with various features used in ALS classifiers and corresponding pathway information. FIG. 22B shows the same feature list with corresponding feature importance based on the best performing models in CV.

FIG. 23 shows self-reported amyotrophic lateral sclerosis treatments.

FIG. 24A shows a table with various features used in ALS classifiers and corresponding pathway information. FIG. 24B shows the same feature list with drugs and/or specific supplements identified for the various metabolites in the feature list.

FIG. 25A shows a map of the AUC performance of 8 different machine learning algorithms or classifiers including the Ensemble classifier when supplements are not excluded from the feature list. FIG. 25B shows an AUC curve for the ALS Ensemble classifier for MS with an AUC of 0.844 with supplements. FIG. 25C shows a map of the AUC performance of 8 different machine learning algorithms or classifiers including the Ensemble classifier when supplements are excluded from the feature list. FIG. 25D shows an AUC curve for the ALS Ensemble classifier with an AUC of 0.908 without supplements. This demonstrates an improvement when supplements are excluded.

FIG. 26 shows an AUC curve for a systemic lupus erythematosus summary score model. The model was trained using 60 SLE positive cases and 320 SLE negative cases (down-sampled). 15 SLE positive cases and 80 SLE negative cases were used for testing. Using a threshold that maximizes true positives, the model calls 0 false negatives out of 15 SLE positive cases (0%) and 28 false positives out of 80 SLE negative cases (35%). Using a threshold that maximizes true negatives, the model calls 5 false negatives out of 15 positive cases (33%) and 0 false positives out of 80 SLE negative cases (0%).

FIG. 27A shows a table with various features used in SLE classifiers and corresponding pathway information. FIG. 27B shows the same feature list with corresponding feature importance based on the best performing models in CV.

FIG. 28 shows self-reported systemic lupus erythematosus treatments.

FIG. 29A shows a table with various features used in SLE classifiers and corresponding pathway information. FIG. 29B shows the same feature list with drugs and/or specific supplements identified for the various metabolites in the feature list.

FIG. 30A shows a map of the AUC performance of 8 different machine learning algorithms or classifiers including the Ensemble classifier when supplements are not excluded from the feature list. FIG. 30B shows an AUC curve for the SLE Ensemble classifier with an AUC of 0.902 with supplements. FIG. 30C shows a map of the AUC performance of 8 different machine learning algorithms or classifiers including the Ensemble classifier when supplements are excluded from the feature list. FIG. 30D shows an AUC curve for the ALS Ensemble classifier with an AUC of 0.845 without supplements. This demonstrates an improvement when supplements are excluded.

FIG. 31 shows an AUC curve for a fibromyalgia classifier. Using a threshold maximizing true positives, the model calls 0 false negatives out of 17 SLE positive cases (0%) and 28 false positives out of 77 SLE negative cases (36%). Using a threshold maximizing true negatives, the model calls 7 false negatives out of 17 SLE positive cases (43%) and 0 false positives out of 77 SLE negative cases (0%).

FIG. 32 shows an exemplary embodiment of a system as described herein.

DETAILED DESCRIPTION

Described herein are devices, software, systems, and methods for assessing an individual for a disease, disorder, or condition by generating a classification relative to a plurality of related classifications based on data obtained from the individual. More specifically, the data comprises metabolite data suitable for detecting at least one of the presence, severity, duration, or status of a disease, disorder, or condition. In some instances, the metabolite data is obtained from a biological sample of the individual and evaluated to determine the presence and/or quantitation of one or more metabolites in the sample. The metabolite data may be obtained multiple times from the individual to enable monitoring over time. The data can also include non-metabolite data such as nucleic acid sequencing and/or expression data. In some cases, the data includes protein or polypeptide data such as expression or quantitation level for a panel of proteins or polypeptides. Machine learning algorithms can be trained to generate classifiers or models that comprise a panel or list of features such as discriminating metabolites or other biomarkers. Multiple machine learning algorithms may be utilized to assess the sample. In some cases, an Ensemble classifier that consolidates two or more machine learning algorithms is used to generate the classification. The classification can include a grade, severity, or class of a particular disease, disorder, or condition. In some embodiments, the systems, devices, software, and methods described herein are configured to identify a diagnostic modality that should be used as an additional step in evaluating an individual who is found by the systems, devices, software, and methods to have a particular disease, disorder, or condition. In some embodiments, the systems, devices, software, and methods described herein are configured to identify a therapy for an individual based on the results of the classification.

Disease Scoring or Classification

In some aspects, described herein are devices, software, systems, and methods for providing disease scoring or classification for an individual based on data such as a molecular profile. An individual's molecular profile can be compared to a broad spectrum of disease, disorder, or condition-associated profiles to generate one or more scores or matches using a classifier or model. The molecular profile can be a metabolite profile comprising one or more metabolites. The metabolites can be associated with one or more metabolic pathways such as, for example, lipid, carbohydrate, or protein metabolism. In some embodiments, the molecular profile comprises a metabolite profile, a protein/polypeptide profile, a gene expression profile, or any combination thereof. In some embodiments, the protein/polypeptide profile comprises quantification or abundance data for one or more proteins or polypeptides. In some embodiments, the gene expression profile comprises RNA sequencing data for one or more biomarkers.

The disease, disorder, or condition-associated profiles can correspond to a plurality of related classifications. In some cases, the related classifications share at least one common feature. In certain aspects, the algorithms described herein provide a classification that stratifies a disease, disorder, or condition. The stratification can be based on severity, grade, class, prognosis, or treatment of a particular disease, disorder, or condition, and/or other relevant factors. In some cases, a subject can be classified for a spectrum of a plurality of diseases, disorders, or conditions, which are optionally further classified into subcategories of the diseases, disorders, or conditions (e.g., subtypes or varying degrees of severity of a disease). For example, autoimmune diseases may be further subcategorized based on biomarkers such as one or more of the metabolite biomarkers disclosed herein.

An individual specimen such as a biological sample can be evaluated to generate a metabolite profile. The metabolite profile can be classified on a spectrum of a plurality of diseases, disorders, or conditions. In some cases, the classification is generated using classifiers trained using one or more machine learning algorithms. Sometimes, the classification comprises a score and/or indicator of the accuracy or confidence of the classification. In certain instances, the score is produced by ensemble machine learning methods, trained to a variety of complex patterns that are tightly associated with disease conditions reported by other individuals or patients. The classification can include a probability that a new sample belongs to a previously learned class of patient-reported outcomes.

The score can be used to evaluate individual disease states and track signs of progress or decline associated with given conditions and interventions, over periods of time. In some cases, a spectrum of multiple classifications are generated for an individual using one or more machine learning algorithms or classifiers. The spectrum of multiple classifications can comprise a plurality of classifications that are related, for example, sharing one or more common predictive features. As an example, MS and ALS share common features, which can lead to misclassification between MS and ALS positive cases. Thus, the generation of a spectrum of multiple classifications can help identify, resolve, and/or mitigate misclassifications between related diseases, disorders, or conditions. In some cases, a spectrum classification comprises a classification between two or more related classifications with a score and/or confidence or likelihood that the individual is positive for one or more of the related classifications. For example, the spectrum classification can be a score indicating a relative likelihood the individual has MS vs ALS (e.g., 35% MS score vs. 65% ALS score). In some instances, the spectrum classification comprises two or more of gastroesophageal reflux disease, bipolar disorder, amyotrophic lateral sclerosis, osteoarthritis, multiple sclerosis, fibromyalgia, systemic lupus erythematosus, generalized anxiety disorder, rheumatoid arthritis, major depressive disorder, high blood pressure hypertension, hypothyroidism, or post-traumatic stress disorder (see FIG. 2A-2B). In some instances, the spectrum classification comprises two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, or thirteen diseases, disorders, or conditions selected from gastroesophageal reflux disease, bipolar disorder, amyotrophic lateral sclerosis, osteoarthritis, multiple sclerosis, fibromyalgia, systemic lupus erythematosus, generalized anxiety disorder, rheumatoid arthritis, major depressive disorder, high blood pressure hypertension, hypothyroidism, or post-traumatic stress disorder.

In some cases, the classifications for the plurality of multiple classification is output as a spectrum of various diseases, disorders, or conditions corresponding to the classifications. The output can be shown as a diagram indicating the score (e.g., as a percentage) of the individual overlaid over the “normal” score range corresponding to non-positive individuals (see FIG. 6A-6B). Thus, the output diagram can provide a simple and intuitive visual indication of whether the individual has or is at risk of developing one or more diseases, disorders, or conditions shown on the diagram. For example, the diagram in FIG. 6B shows that the individual has an osteoarthritis score that exceeds the normal range, thereby indicating the individual has or is at risk of developing osteoarthritis. Such diagrams are also useful for monitoring an individual over time, for example, allowing a simple visualization of an increase or decrease in score for a particular disease over time.

Metabolite profiles can be generated for two or more specimens obtained from an individual over a period of time. The metabolite profiles can be evaluated using the methods described herein to generate a classification or a spectrum of related classifications. The classification or spectrum of related classifications can be compared between specimens to assess an individual over a period of time. The period of time can be at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60 minutes and/or no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60 minutes. In some cases, the period of time is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours and/or no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 hours. In certain instances, the period of time is at least 1, 2, 3, 4, 5, 6, or 7 days and/or no more than 1, 2, 3, 4, 5, 6, or 7 days. The period of time can be at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, or 52 weeks and/or no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, or 52 weeks. Sometimes, the period of time is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 years and/or no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 years.

The accuracy, specificity, sensitivity, positive predictive value, negative predictive value, or any combination thereof may be determined for a classifier by testing it against a set of independent samples. True positive (TP) is a positive test result that detects the condition when the condition is present. True negative (TN) is a negative test result that does not detect the condition when the condition is absent. False positive (FP) is a test result that detects the condition when the condition is absent. False negative (FN) is a test result that does not detect the condition when the condition is present. Accuracy is defined by the formula: accuracy=(TP+TN)/(TP+FP+FN+TN). Specificity (“true negative rate”) is defined by the formula: specificity=TN/(TN+FP). Sensitivity (“true positive rate”) is defined by the formula: sensitivity=TP/(TP+FN). Positive predictive value (PPV or “precision”) is defined by the formula: PPV=TP/(TP+FP). Negative predictive value (NPV) is defined by the formula: NPV=TN/(TN+FN).

In some cases, an individual or sample is classified with respect to one or more diseases, disorders, or conditions with an accuracy of at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% for at least 100, 150, or 200 independent samples. In some cases, an individual or sample is classified with respect to one or more diseases, disorders, or conditions with an specificity of at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% for at least 100, 150, or 200 independent samples. In some cases, an individual or sample is classified with respect to one or more diseases, disorders, or conditions with a sensitivity of at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% for at least 100, 150, or 200 independent samples. In some cases, an individual or sample is classified with respect to one or more diseases, disorders, or conditions with an AUC of at least about 0.80, 0.85 0.90, 0.95, 0.96, 0.97, 0.98, or 0.99 for at least 100, 150, or 200 independent samples.

Health data of an individual presented to a healthcare provider by the systems, media, or methods as described herein may include the diagnoses or classification, treatment regimen, and/or outcome of the individual. Non-limiting examples of health data presented to a healthcare provider may include metabolite data, classification, other data such as non-molecular/metabolite data, and therapeutic options.

In some embodiments an insight generated by the systems, media, or methods as described herein comprises one or more treatment regimens. For example, the system may present a treatment regimen to a healthcare provider that was deemed successful for subjects having metabolite profiles similar to that of the individual evaluated according to the systems, media, and methods described herein. A treatment regimen may be deemed successful, in some embodiments, when a goal of the patient is achieved through the application of the treatment regimen. An example of a treatment is diet, exercise, and statins for an individual determined to be overweight or obese and having atherosclerosis or heart disease.

Diseases, Disorders, and Conditions

Disclosed herein are algorithms, classifiers, or models that generate classifications of individuals based on input data. The classifications can correspond or relate to one or more diseases, disorders, or conditions. A disease can be identified as abnormalities or dysfunctions in systemic functions. A disorder can be identified as a disruption of the normal functions of the body. Accordingly, a disorder can be the resulting disruption caused by a disease in certain cases. A condition can be identified as an abnormal state of health, including states that interfere with normal activities or well-being of the individual. These categories may exhibit some overlap.

In some cases, the classification corresponds or relates to a neurological and/or autoimmune disease such as, for example, multiple sclerosis, systemic lupus erythematosus, or amyotrophic lateral sclerosis.

In some cases, the systems, media and methods disclosed herein provide a prediction or recommendation for treatment based on the classification or evaluation of one or more diseases, disorders, or conditions. In some cases, a report is generated comprising one or more findings such as the results of the classification or evaluation. In some cases, the report comprises or more diagnoses. In some cases, the report comprises one or more treatments or treatment recommendations. In some cases, the methods disclosed herein comprise providing treatment to the subject. In some instances, treatment is provided based at least on the classification or evaluation. The treatment can be a particular treatment for the one or more diseases, disorders, or conditions, for example, autoimmune diseases or disorders may be treated using an anti-inflammatory medication (e.g., acetaminophen, NSAIDs such as ibuprofen), corticosteroids (e.g., hydrocortisone, dexamethasone, prednisone, methylprednisolone, betamethasone), antimalarial drugs for skin and joint problems (e.g., hydroxychloroquine), immunosuppressants (e.g., azathioprine, mycophenolate mofetil, methotrexate), biologics such as antibodies (e.g., belimumab for treating SLE, and rituximab for treating MS, SLE, etc.), or any combination thereof. In some cases, the treatment comprises a drug treatment. Alternatively or in combination, the treatment comprises lifestyle changes such as to diet and/or exercise, or other non-pharmaceutical therapies. In some cases, the treatment comprises a drug treatment or therapy for a single disease, disorder, or condition identified according to the present disclosure. In some cases, the treatment comprises one or more drug treatments or therapies for multiple related diseases, disorders, or conditions.

In some cases, the treatment or treatment recommendation is generated for a subject who has not undergone treatment. In some cases, the subject is undergoing treatment and/or has previously been treated. In some cases, the classification or evaluation of a subject for one or more diseases, disorders, or conditions is used to monitor responsiveness to the treatment. For example, an algorithm or model that generates a result indicating severity or severity category for a disease, disorder, or condition may be used to evaluate a subject over time to determine whether the subject is responding to ongoing treatment as indicated by a decrease in severity over time. Accordingly, the systems and methods disclosed herein can include recommendations or steps to continue current treatment or therapy, cease treatment or therapy, or change/modify the current treatment or therapy (e.g., by changing a dose or adding another treatment).

In some instances, the systems and methods disclosed herein provide treatment(s) or treatment recommendation(s) for one or more diseases, disorders, or conditions selected from gastroesophageal reflux disease (e.g., antacids, H-2 receptor blockers such as cimetidine, famotidine, nizatidine, ranitidine, proton pump inhibitors such as esomeprazole, lansoprazole, omeprazole, pantoprazole, surgery), bipolar disorder (e.g., mood stabilizers such as valproic acid, antipsychotics such as Haldol decanoate, aripiprazole, olanzapine, risperidone, antidepressants such as selective serotonin reuptake inhibitors, citalopram, fluoxetine, paroxetine), amyotrophic lateral sclerosis (e.g., riluzole, edavarone, physical therapy, speech therapy), osteoarthritis (e.g., acetaminophen, NSAIDs, duloxetine, corticosteroids, surgery, physical therapy), multiple sclerosis (e.g., corticosteroids, such as prednisone and methylpredinisone, plasmapheresis, beta interferons, glatiramer acetate, fingolimod, teriflunomide, biologics such as ocrelizumab, natalizumab, alemtuzumab), fibromyalgia (acetaminophen, NSAIDs, antidepressants such as duloxetine, milnacipran, cyclobenzaprine, anti-seizure drugs such as gabapentin, pregabalin, physical therapy), systemic lupus erythematosus (acetaminophen, NSAIDs, steroid creams, corticosteroids, antimalarial drugs, immunotherapies), generalized anxiety disorder (e.g., antidepressants such as escitalopram, duloxetine, venlafaxine, paroxetine), rheumatoid arthritis (e.g., acetaminophen, NSAIDs, corticosteroids such as prednisone, disease modifying antirheumatic drugs (DMARMs) such as methotrexate, biologics such as adalimumab, certolizumab, etanercept, golimumab, occupational therapy, surgery), major depressive disorder (e.g., SSRIs, SNRIs, antidepressants, MAOIs), high blood pressure hypertension (e.g., angiotensin converting enzyme (ACE) inhibitors, beta-blockers, calcium channel blockers, alpha-blockers, alpha-agonists, renin inhibitors diuretics), hypothyroidism (e.g., synthetic levothyroxine), or post-traumatic stress disorder (e.g., antidepressants, anti-anxiety medication, prazosin, cognitive therapy, exposure therapy). Although an exhaustive list of pharmaceutical and non-pharmaceutical treatments is not provided for every disease, disorder, or condition described herein, the present disclosure contemplates any treatment known in the field for the diseases, disorders, or conditions including but not limited to treatments for those diseases, disorders, or conditions recited in Table 1.

The classifications can comprise conditions that are not necessarily associated with disease states. For example, a classification can include obesity, sleep deprivation, lack of exercise, oral health status, sleep apnea, and other health status indicators.

TABLE 1
shows non-limiting examples of diseases, disorders, and conditions.
abdominal adhesions
abdominal migraine
abdominal wall schwannoma
acanthosis nigricans
accidental fall
Achilles tendonosis
achondroplasia
ACL (anterior cruciate
ligament) injury
acne
acoustic neuroma
acquired brain injury
acquired deformity of the
ankle
actinic keratosis
acute angle-closure glaucoma
acute pericarditis
acute renal failure
acute respiratory distress
syndrome
Addison's disease
adenocarcinoma (non-small
cell lung cancer)
adenomyosis
adenosquamous carcinoma
(non-small cell lung cancer)
adjustment disorder
adrenal adenoma
adrenal exhaustion
adrenal fatigue
adrenal insufficiency
adult apraxia of speech
aging
agoraphobia
Aicardi-Goutieres syndrome
alcohol use disorder
alexithymia
allergic asthma
allergic fungal sinusitis
allergic rhinitis
alopecia areata
alopecia universalis
alpha 1 antitrypsin deficiency
alternating hemiplegia of
childhood
amyotrophic lateral sclerosis
anaesthesia dolorosa
anal fistula
anaphylaxis
anatomically narrow angle
glaucoma
anatomically narrow angle
without glaucoma
androgen deficiency
anemia of chronic disease
angina pectoris
angulation of the coccyx
anhidrosis
ankle sprain
ankylosing spondylitis
anorexia nervosa
anorexia nervosa binge eating
purging type
anti-myelin associated
glycoprotein polyneuropathy
antiphospholipid antibody
syndrome
antisocial personality disorder
aortic aneurysm
aortic valve disorder
aortic valve regurgitation
aphakia
appendicitis
appendix cancer
arachnoid cyst
arachnoiditis
arachnophobia
arrhythmogenic right
ventricular dysplasia
asbestosis
ascending cholangitis
Asperger's syndrome
aspiration pneumonia
aspirin induced asthma
asthma
astigmatism
atherosclerosis
atlantoaxial subluxation
atopic dermatitis
atrial fibrillation
atrial flutter
atrial septal defect
atrial tachycardia
attention deficit disorder
attention deficit/hyperactivity
disorder
atypical choroid plexus
papilloma
atypical depressive disorder
atypical facial pain
atypical hyperplasia of breast
atypical migraine
auditory processing disorder
autism spectrum disorder
autoimmune disease undefined
autoimmune hemolytic anemia
autoimmune hepatitis
autoimmune inner ear disease
autoimmune neutropenia
autoimmune pancreatitis
autoimmune progesterone
dermatitis
autoimmune urticaria
autoimmune vasculitis
autonomic neuropathy
avoidant personality disorder
azygos vein stenosis
B cell prolymphocytic
leukemia
Baastrup syndrome
bacterial conjunctivitis
bacterial overgrowth syndrome
bacterial vaginosis
Baker's cyst
balanced translocation
Barre-Lieou syndrome
Barrett's esophagus
basal cell skin cancer
battered person syndrome
Behcet's disease
Bell's palsy
below knee amputation (left)
below knee amputation (right)
benign adrenal tumor
benign brain tumor
benign breast tumor
benign fasciculation syndrome
benign ovarian tumor
benign paroxysmal positional
vertigo
benign prostatic hyperplasia
benign retroperitoneal
schwannoma
benzodiazepine withdrawal
syndrome
bicep rupture
bicuspid aortic valve
bilateral vestibular
hypofunction
bile duct obstruction
biliary reflux
binge eating disorder
bipolar disorder
bipolar I disorder
bipolar II disorder
Birt-Hogg-Dube syndrome
BK virus
bladder cancer
bladder infection (infective
cystitis)
bladder ulcer
blepharitis
body dysmorphic disorder
bone marrow transplant
bone necrosis
bone spurs
borderline personality disorder
bowel obstruction
brachial plexus neuroma
brachioradial pruritus
brain aneurysm
brain damage in infancy
brain stem lesion
brain tumor
breast cancer
breast papilloma
broken ankle
broken arm (left)
broken arm (right)
broken clavicle
broken elbow (left)
broken elbow (right)
broken eye socket
broken foot
broken hand
broken hip (left)
broken hip (right)
broken jaw
broken knee
broken leg (left)
broken leg (right)
broken neck
broken nose
broken pelvis
broken ribs
broken shoulder
broken spine
broken toes
broken wrist
bronchiectasis
bronchiolitis obliterans
bronchitis
Brugada syndrome
bulimia nervosa
bullous emphysema
bullous pemphigoid
bundle branch block (right)
bunion
burning mouth syndrome
bursitis
burst fracture of spine
C. diff (Clostridium difficile)
infection
candida (fungal) infection
car accident
carbon monoxide poisoning
cardiac arrest
cardiogenic shock
cardiomegaly
cardiomyopathy
carotid artery aneurysm
carotid artery dissection
carpal tunnel syndrome
cataplexy
cataracts
celiac disease
cellulitis
central pain syndrome
central sensitivity syndrome
central serous choroidopathy
central sleep apnea
central vertigo
cerebellar ataxia
cerebellar ataxia-neuropathy-
vestibular areflexia syndrome
cerebral arteriovascular
malformation
cerebral atrophy
cerebral malformation
cerebral palsy
cerebral small vessel disease
cerebral venous thrombosis
cerebrospinal fluid leak
cervical cancer
cervical dysplasia
cervical facet syndrome
cervical radiculopathy
cervical spondylosis
cervical vertebral subluxation
cervicitis
cervicogenic headache
cevical kyphosis
Charcot-Marie-Tooth disease
chemical menopause
chemical/venom allergy
Chiari malformation
chickenpox
chilblains
cholecystitis
cholesteatoma
cholinergic urticaria
chondromalacia patellae
chronic abdominal pain
syndrome
chronic cerebrospinal venous
insufficiency
chronic cutaneous lupus
erythematosus
chronic diastolic heart failure
chronic Epstein-Barr
chronic headache disorder
chronic hyperglycemia
chronic idiopathic back pain
Chronic Idiopathic
Constipation
chronic idiopathic hives
chronic inflammatory
demyelinating polyneuropathy
chronic inflammatory response
syndrome
chronic kidney disease
chronic lymphocytic leukemia
chronic mercury poisoning
chronic neuralgia
chronic obstructive bronchitis
chronic obstructive pulmonary
disease
chronic pain syndrome
chronic pelvic pain syndrome
chronic pericarditis
chronic periodontitis
chronic recurrent multifocal
osteomyelitis
chronic respiratory failure
chronic thromboembolic
pulmonary hypertension
circadian rhythm sleep
disorder
claustrophobia
cluster headaches
CNS lupus
cold sore (herpes simplex)
cold urticaria
colloid cysts
colon cancer
color blindness
coma
common variable
immunodeficiency disorder
complex confusional migraine
complex migraine
complex post-traumatic stress
disorder
complex regional pain
syndrome type I
complex regional pain
syndrome type II
complicated grief
compression fracture of spine
compulsive gambling
concussion
congenital afibrinogenemia
congenital anosmia
congenital cervical fusion
congenital disorders of
glycosylation
congenital muscular dystrophy
with arthrogryposis multiplex
congenita
congenital nystagmus
congenital rubella
congenital spinal stenosis
congestive heart failure
Conn's syndrome
conversion disorder
corneal abrasion
corneal map-dot-fingerprint
dystrophy
coronary artery disease
cortical blindness
corticobasal degeneration
costochondritis
cough variant asthma
CREST syndrome
critical illness polyneuropathy
Crohn's disease
cryptococcal pneumonia
cryptogenic cirrhose
cryptogenic organizing
pneumonia
cubital tunnel syndrome
Cushing's disease
Cushing's syndrome
cyclic vomiting syndrome
cyclical neutropenia
cyclothymia
cystic fibrosis
cystic fibrosis-related diabetes
cystocele
cytomegalovirus
DCIS (Ductal carcinoma in
situ)
de Quervain syndrome
decompression sickness
deep vein thrombosis
degenerative disc disease
degenerative myopia
delayed sleep phase syndrome
demyelinating disease of
central nervous system
dengue
dental cavities
dentinogenesis imperfecta
dependent personality disorder
depersonalization disorder
Dercum's disease
dermatillomania
dermatographism
dermatomyositis
desquamative interstitial
pneumonia
developmental delay
developmental language
disorder
developmental trauma disorder
developmental venous
anomaly
deviated nasal septum
diabetes insipidus
diabetes type 1
diabetes type 2
diabetic ketoacidosis
diabetic neuropathy
diabetic retinopathy
diastolic dysfunction
diffuse idiopathic skeletal
hyperostosis
dilated cardiomyopathy
discoid lupus erythematosus
discoid meniscus
dislocated elbow (left)
dislocated thumb
dislocation of hip (left)
disruptive mood dysregulation
disorder
dissociative identity disorder
diverticulitis
diverticulosis
DRESS syndrome
drug use disorder
dry eye syndrome
Duchenne muscular dystrophy
duodenal ulcer
Dupuytren's contracture
dysarthria
dysautonomia
dyshidrotic eczema
dyslexia
dysmenorrhea
dyspareunia
dysphasia
dystonia
E. coli infection
early onset dementia
eating disorder
Ebstein's anomaly
ectopic pregnancy
eczema
Ehlers-Danlos syndrome
elbow schwannoma
emphysema
encephalitis
endocarditis
endometrial cancer
endometrial intraepithelial
neoplasia
endometriosis
eosinophilic esophagitis
eosinophilic polymyositis
epigastric hernia
epilepsy
episcleritis
episodic ataxia
erectile dysfunction
erosive osteoarthritis
erythromelalgia
esophageal achalasia
esophageal diverticulum
esophageal dysphagia
esophageal spasms
esophagitis
essential myoclonus
essential thrombocythemia
essential tremor
eustachian tube dysfunction
Evans syndrome
exotropia
facet joint osteoarthritis
factor V Leiden
factor VIII elevation
factor XIII deficiency
failed back syndrome
familial adenomatous
polyposis
familial hypercholesterolemia
familial mediterranean fever
fat malabsorption
female infertility
female pattern baldness
femoral acetabular
impingement-cam type
femoral anteversion
femoral hernia
fibrocystic breast tissue
fibromuscular dysplasia
fibromyalgia
fibrous dysplasia
finger amputation
flat feet (pes planus)
focal dystonia
folate deficiency anemia
follicular thyroid cancer
food additive allergy
food allergy
foot schwannoma
foot stress fracture
foreign accent syndrome
fractured calcaneus
fractured fingers
fractured tailbone
frontal fibrosing alopecia
frontotemporal dementia
fructose malabsorption
Fuchs' dystrophy
functional dyspepsia
functional movement disorder
functional neurologic symptom
disorder
fungal meningitis
gallstones
ganglion cyst
gastric antral vascular ectasia
gastric ulcer
gastritis
gastroesophageal reflux
disease
gastrointestinal fistula
gastrointestinal polyps
gastroparesis
gastroschisis
gender dysphoria
generalized anxiety disorder
genital herpes
Gilbert's syndrome
gingivitis
Glanzmann's thrombasthenia
glaucoma
glioblastoma
glomerulonephritis
glomus tympanicum jugulare
paraganglioma
glossopharyngeal neuralgia
glucose 6 phosphate
dehydrogenase deficiency
glucose transporter type 1
deficiency
glycogen storage disease
gonorrhea
gout
granuloma annulare
granulomatosis with
polyangiitis (Wegener's)
Graves' disease
growth hormone deficiency
gynecomastia
H. pylori
H1N1 influenza A
Haglund's deformity
hallux rigidus
Hashimoto encephalitis
Hashimoto's thyroiditis
head contusion
hearing loss
heart attack (myocardial
infarction)
heart block
heart failure
heart murmur
heart transplant
heavy metal toxicity
hemifacial spasm
hemiplegia
hemiplegic migraine
hemochromatosis
hemolytic anemia
hemophilia A
hemorrhoids
hepatic encephalopathy
hepatitis B
hepatitis C
hereditary fructose intolerance
hereditary hemorrhagic
telangiectasia
hereditary spastic paraplegia
hereditary spherocytosis
herniated disc
herpes simplex virus infection
herpes zoster ophthalmicus
hiatal hernia
hidradenitis suppurativa
high arches (pes cavus)
high blood pressure
(hypertension)
high cholesterol
(hypercholesterolemia)
hip bursitis
hip disarticulation (right)
hip dysplasia
hip labral tear
histamine intolerance
(histaminosis)
histoplasmosis
hormonal imbalance
human immunodeficiency
virus (HIV)
human papillomavirus
infection
Huntington's disease
hydrocephalus
hyperacusis
hypercalcemia
hyperhidrosis disorder
hyperinsulinemia
hyperinsulinemic
hypoglycemia with
nesidioblastosis
hyperkalemia
hyperkyphosis
hyperlipidemia
hypermobility syndrome
hyperparathyroidism
hypersensitivity pneumonitis
hypersensitivity vasculitis
hyperthyroidism
hypertonic pelvic floor
dysfunction
hypertriglyceridemia
hypertrophic obstructive
cardiomyopathy
hypochondria
hypogammaglobulinemia
hypogonadism
hypokalemia
hypokalemic periodic paralysis
hypomania
hypoparathyroidism
hypotension
hypothyroidism
hypoxemia
ice pick headache
idiopathic adhesive capsulitis
idiopathic angioedema
idiopathic hypersomnia
idiopathic intracranial
hypertension
idiopathic leukocytosis
idiopathic polymorphic
ventricular tachycardia
idiopathic pulmonary arterial
hypertension
idiopathic pulmonary fibrosis
idiopathic thrombocytopenia
purpura
IgA deficiency
IgA nephropathy
IgE deficiency
IgG deficiency
iliac vein compression
syndrome
iliotibial band syndrome
inappropriate sinus tachycardia
inclusion body myositis
indeterminate colitis
indolent systemic mastocytosis
infection of uncertain origin
infectious colitis
inferior alveolar nerve damage
influenza (the “flu”)
infracalcaneal bursitis
ingrown hair
inguinal hernia
inherited pressure palsy
neuropathy
insomnia
internal jugular vein stenosis
internuclear ophthalmoplegia
intersex
interstitial cystitis
interstitial lung disease
intestinal arteriovenous
malformation
intracranial hemorrhage
invasive lobular carcinoma
iritis
Irlen syndrome
iron deficiency anemia
irritable bladder syndrome
irritable bowel syndrome
ischemia stroke
ischemic colitis
jock itch
keloid scar
keratitis
keratoconus
keratosis pilaris
kidney cyst
kidney stone
kidney transplant
kidney transplant rejection
Kikuchi disease
Klinefelter syndrome
knee injury
kneecap (patellar) dislocation
knock kneed
kyphoscoliosis
labile hypertension
labyrinthitis
lactose intolerance
laryngeal cancer
laryngopharyngeal reflux
leaky gut syndrome
Leber's optic atrophy
left ventricular hypertrophy
left ventricular systolic
dysfunction
leukopenia
Lewy body disease
lichen planus
lichen sclerosus
lichen simplex chronicus
lipedema
lipoma(s)
liver cirrhosis
liver cysts
liver enlargement
liver impairment
liver toxicity
Lobular Carcinoma In Situ
logopenic progressive aphasia
long qt syndrome
longsightedness
lordosis
loss of loved one
low calcium (hypocalcemia)
lumbar disc annular tear
lumbar radiculopathy
lumbar spondylosis
lumbosacral radiculopathy
lung collapse (atelectasis)
lung nodules
lung transplant
lupus nephritis
lupus pneumonitis
lupus profundus
Lyme disease
lymphedema
lymphomatoid papuplosis
macular degeneration
macular drusen
macular edema
macular fibrosis
major depressive disorder
maladaptive daydreaming
malignant hyperthermia
Marfan syndrome
mast cell activation syndrome
mastitis
math learning disability
medial collateral ligament tear
medial epicondylitis
medullary sponge kidney
medullary thyroid cancer
meibomian gland dysfunction
melanoma
melorheostosis
Meniere's disease
meningioma
menopause
menorrhagia
meralgia paresthetica
metabolic syndrome
metal allergy
metallosis
metastatic melanoma
metathesiophobia
methicillin-resistant
Staphylococcus aureus
methylenetetrahydrofolate
reductase deficiency
microscopic colitis
microvascular angina
microvascular disease
mid foot sprain
migraine
migraine with brainstem aura
mild depression
military sexual trauma
miscarriage
mitochondrial disease
mitral valve disorder
mitral valve prolapse
mitral valve regurgitation
mitral valve stenosis
mixed connective tissue
disease
mixed tension migraine
Mollaret's meningitis
monoclonal gammopathy of
undetermined significance
mononucleosis
Morton's neuroma
mosaic 13q12.2-34 deletion
mucous cyst
multifocal motor neuropathy
multiple chemical sensitivity
multiple myeloma
multiple sclerosis
multiple system atrophy
mumps
muscle tension dysphonia
muscular dystrophy
musculocutaneous neuropathy
myalgic
encephalomyelitis/chronic
fatigue syndrome
myasthenia gravis
mycobacterium avium
complex
myelopathy
myeloproliferative disorder
myoclonic dystonia
myofascial pain syndrome
myopathy
myositis
nail fungus
narcolepsy
nasal polyps
nasal turbinate hypertrophy
natural killer cell deficiency
syndrome
nephropathy C1q
nervous breakdown
neurally mediated hypotension
neuroendocrine tumor
neurofibromatosis
neurogenic bladder
neurogenic bowel disorder
neuromyelitis optica
neurosarcoidosis
nevus anemicus
new daily persistent headache
nightmare disorder
non-alcoholic fatty liver
disease
non-allergic rhinitis
non-celiac gluten intolerance
non-diabetic hypoglycemia
non-Hodgkin's lymphoma
non-progressive mild cognitive
impairment
non-small cell lung cancer
nonalcoholic steatohepatitis
nondiabetic lumbosacral
radiculoplexus neuropathy
nonverbal learning disability
normal pressure hydrocephalus
Nutcracker syndrome
obesity
obsessive compulsive hoarding
disorder
obsessive compulsive
personality disorder
obsessive-compulsive disorder
obstructive sleep apnea
occipital neuralgia
ocular hypertension
ocular migraine
ophthalmic rosacea
optic disc drusen
optic neuritis
oral allergy syndrome
oral lichen planus
organic brain syndrome
orthostatic hypotension
ossification of the posterior
longitudinal ligament
osteoarthritis
osteogenesis imperfecta
osteomyelitis
osteopenia
osteoporosis
other specified dissociative
disorder
otosclerosis
ovarian cancer
ovarian cyst
ovarian torsion
overeating disorder
Paget-Schroetter syndrome
Paget's disease of bone
painful legs and moving toes
syndrome
palmoplantar pustulosis
pancreas divisum
pancreatic insufficiency
pancreatitis
pancreatogenous diabetes
panhypopituitarism
panic disorder
papillary thyroid carcinoma
papilledema
paranoid personality disorder
paranoid schizophrenia
paraovarian cysts
Parkinson's disease
parotid gland tumor
paroxysmal dyskinesia
passive aggressive personality
disorder
patellar tracking disorder
patellofemoral pain syndrome
patent foramen ovale
pattern macular dystrophy
pelvic congestion syndrome
pelvic floor dyssynergia
pelvic inflammatory disease
pelvic organ prolapse
pelvic schwannoma
pelvic torsion
pemphigus
perennial allergy
pericardial cyst
pericardial effusion
perimenopause
perineal laceration during
childbirth
periodic limb movement
disorder
periodontal disease
perioral dermatitis
peripheral arterial disease
peripheral neuropathy
peripheral retinal degeneration
pernicious anemia
persistent depressive disorder
(dysthymia)
personality disorder
petechiae
phimosis
phleboliths
phobic disorder
photodermatitis
phyllodes tumor
pigmentary dispersion
syndrome
pineal gland cyst
piriformis syndrome
pituitary adenoma
pituitary deficiency
placenta accreta
placenta percreta
placenta previa
plantar fascial fibromatosis
plantar fasciitis
pleural effusion
pleurisy
pneumonia
poikilothermia
polyarteritis nodosa
polyarticular onset juvenile
arthritis
polycystic kidney disease
polycystic ovary syndrome
polycythemia vera
polymyalgia rheumatica
polymyositis
portal hypertension
post intensive care unit
syndrome
post-polio syndrome
post-concussion syndrome
post-surgical malabsorption
post-traumatic headache
post-traumatic stress disorder
post-treatment Lyme disease
syndrome
posterior cruciate ligament
injury
posterior tibial tendon
dysfunction
postherpetic neuralgia
postmenopause
postpartum depression
postpartum psychosis
postural orthostatic tachycardia
syndrome
pre-glaucoma
prediabetes
preeclampsia/eclampsia
pregnancy
prehypertension
premature atrial contractions
premature birth
premature menopause
premature ovarian failure
premature ventricular
contractions
premenstrual dysphoric disorder
primary amenorrhea
primary biliary cholangitis
primary hyperhidrosis
primary lateral sclerosis
primary orthostatic tremors
primary progressive aphasia
primary spontaneous
pneumothorax
Prinzmetal angina
progressive bulbar palsy
progressive muscular atrophy
progressive supranuclear palsy
prolactinoma
prosopagnosia
prostate cancer
protein S deficiency
prothrombin 20210 mutation
thrombophilia
proximal myopathy
proximal neuropathy
pseudocyst
pseudodementia
psoriasis
psoriatic arthritis
psychogenic non-epileptic
seizures
psychosis disorder
psychotic depression
pulmonary aneurysm
pulmonary edema
pulmonary embolism
pulmonary fibrosis
pulmonary hypertension
pulmonary sarcoidosis
pulmonary toxicity
pulmonary valve stenosis
pure autonomic failure
pyloric stenosis
pyroluria syndrome
quadriplegia
radiation exposure
radiculopathy
rage disorder
Rathke cleft cyst
Raynaud's disease
reactive airways dysfunction
syndrome
reactive arthritis
reactive attachment disorder
reactive depression
reactive hypoglycemia
reactive thrombocytosis
rectal outlet dysfunction
rectal prolapse
rectocele
red skin syndrome/topical
steroid withdrawal
redundant colon
REM sleep behavior disorder
renal artery stenosis
renal cell cancer
repetitive stress injury
residual schizophrenia
respiratory syncytial virus
(RSV) infection
restless legs syndrome
restrictive lung disease
retained placenta
retinal detachment
retroperitoneal hernia
Reynolds syndrome
rhabdomyolysis
rheumatic fever
rheumatoid arthritis
rheumatoid lung disease
rib dysfunction
rocky mountain spotted fever
rosacea
rotator cuff syndrome
rupture of colon
rupture of spleen
ruptured hand tendon
sacroiliac joint dysfunction
sacroiliitis
salivary gland cancer
sarcoidosis
Scheuermann, Äôs kyphosis
schizoaffective disorder
schizoid personality disorder
schizophrenia
Schmorl's nodes
schwannoma of spinal cord
sciatic neuralgia
scleroderma
scoliosis
seasonal affective disorder
seasonal allergy
seborrheic dermatitis
Seborrheic Psoriasis
secondary hypogonadism
secondary immunodeficiency
disorder
secondary polycythemia
sensory processing disorder
separation anxiety disorder
sepsis
serotonin deficiency syndrome
serotonin syndrome
severe combined
immunodeficiency disease
sex addiction
sexual abuse
shared psychotic disorder
shingles (herpes zoster)
shortsightedness
shoulder injury
shoulder subluxation
SIADH
sialolithiasis
sickle cell disease
silent migraine
sinus bradycardia
sinus infection (sinusitis)
sinus node dysfunction
sinus tachycardia
sinus tarsi syndrome
Sjogren-Larsson syndrome
Sjogren's syndrome
skull fracture
sleep apnea disorder
sleep paralysis
sleep walking (somnambulism)
slow transit constipation
small cell lung cancer
small fiber sensory neuropathy
snapping hip disorder
social anxiety disorder
solar urticaria
somatization disorder
spasmodic dysphonia
spastic diplegia cerebral palsy
species dysphoria
speech disorder
sphenoid sinusitis
sphincter of Oddi dysfunction
spina bifida
spina bifida occulta
spinal accessory nerve injury
spinal cord injury
spinal hemangioma
spinal meningitis
spinal myoclonus
spinal stenosis
splenic artery aneurysm
splenomegaly
spondyloarthropathy
spondylolisthesis
spondylosis
squamous cell skin cancer
statin-induced myopathy
status migrainosus
steroid-induced diabetes
mellitus
steroid-induced myopathy
Stevens Johnson syndrome
stiff person syndrome
stillbirth
stomach cancer
stomach flu (gastroenteritis)
storage pool disease
strabismus amblyopia
strep throat
stroke
subacute cutaneous lupus
erythematosus
subacute thyroiditis
subdural hematoma
superior mesenteric artery
syndrome
supraventricular tachycardia
surgical menopause
Sweet syndrome
synovial cyst
syringomyelia
systemic candidiasis
systemic inflammatory response
syndrome
systemic lupus erythematosus
Systemic Mast Cell Disorder
(SMCD)
systemic onset juvenile arthritis
systemic vasculitis
tailor's bunion
tardive dyskinesia
Tarlov cyst
tarsal tunnel syndrome
telangiectasia macularis
eruptiva perstans
telangiectasias
temporal arteritis
temporomandibular joint disc
dislocation
temporomandibular joint
syndrome
tendinitis
tendinopathy
tendonosis
tennis elbow (lateral
epicondylitis)
tenosynovitis
tension headache
terminal esophageal web
testicular cancer
tethered cord syndrome
thalassemia
third degree burns
thoracic outlet syndrome
thoracic radiculopathy
thoracic spondylosis
thrombocytopathy
thrombotic thrombocytopenia
purpura
thyroid cancer
thyroid nodule
Tietze's syndrome
tinea corporis
tinnitus
tobacco use disorder
toe amputation (left)
toe amputation (right)
tonsillitis
tooth abscess
tooth fractures
torn meniscus of knee
torticollis
Tourette syndrome
toxic encephalopathy
toxoplasmosis
tracheobronchomalacia
transient ischemic attack
transient osteoporosis of hip
transverse myelitis
traumatic brain injury
trichotillomania
tricuspid valve regurgitation
trigeminal neuralgia
trimalleolar fracture
tuberculosis
Turner's syndrome
twisted bowel (intestinal
volvulus)
typhlitis
ulcerative colitis
ulnar tunnel syndrome
umbilical hernia
undifferentiated connective
tissue disease
undifferentiated inflammatory
arthritis
unilateral vestibular
hypofunction
unspecified dissociative
disorder
upper airway resistance
syndrome
urethral stricture
urge incontinence
urinary incontinence
urinary tract infection
urosepsis
uterine cancer
uterine fibroids
uterine polyp
uveitis
vaginismus
vagus nerve schwannoma
valvular heart disease
varicose veins of legs
vasovagal syncope
venous insufficiency
ventral hernia
ventribular fibrillation
ventricular septal defect
ventricular tachycardia
vestibular migraine
viral meningitis
vision loss
vitamin A deficiency
vitamin B12 deficiency
vitamin B2 deficiency
vitamin B6 deficiency
vitamin D deficiency
vitiligo
vocal cord dysfunction
vocal cord pharyngeal distal
myopathy
von Willebrand disease
vulvar vestibulitis
vulvodynia
West Nile virus
whiplash
white matter disease
whooping cough
Wolff-Parkinson-White
syndrome
written expression learning
disability
xanthelasma

Biological Samples

In some aspects, the algorithms, models, or classifiers described herein utilize data derived from biological samples. Biological samples include any biological material from which biomolecules such as metabolites can be prepared and examined. Non-limiting examples include whole blood, plasma, saliva, cheek swab, fecal material, urine, cell mass, biopsy, or any other bodily fluid or tissue.

Metabolites

In some aspects, the algorithms, models, or classifiers described herein are configured to generate a classification or a spectrum of related classifications based on data such as metabolite data. The metabolite data can be obtained from a biological sample of an individual using various molecular detection techniques described herein. The metabolites can be implicated in one or more metabolic pathways. Metabolites include small molecules present in the cells, tissues, organs, and/or fluids that are involved in metabolism. A metabolite can be an intermediate end product of a metabolic pathway or process. Metabolites can have various functions, including use as a source of energy (e.g., ATP), a metabolic building block (e.g., acetyl coenzyme A), signaling, and other molecular pathways.

Metabolites can include components of biochemical classes of molecules such as amino acids, monosaccharides, nucleotides, and fatty acids/glycerol and other building blocks of proteins, carbohydrates, nucleic acids, and lipids, respectively. Metabolites can include coenzymes such as adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NADH or NADPH) which play roles in various biochemical anabolic and catabolic reactions. Table 2 shows a non-limiting list of metabolites that can be evaluated by the algorithms described herein to generate one or more classifications of diseases, disorders, or conditions. In some cases, the panel of biomarkers used to classify or evaluate the status of a disease, disorder, or condition as disclosed herein comprises one or more metabolites selected from Table 2. In some cases, the panel of biomarkers comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 19, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, or 950 or more metabolites from Table 2. In some cases, the panel of biomarkers comprises no more than 1, 2, 3, 4, 5, 6, 7, 8, 19, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, or 950 or more metabolites from Table 2. In some embodiments, the panel of biomarkers comprises a subset of metabolites selected from Table 2 that satisfy a threshold or performance metric as disclosed herein, for example, a correlation or association with one or more diseases, disorders, or conditions of interest having a certain p-value or metric such as PPV or AUC.

TABLE 2
Probe name	platform	data_type	official_symbol	EGID/COMP_ID
mlon_1101	mlon	metabolomics	homovanillate (HVA)	1101
mlon_1105	mlon	metabolomics	linoleate (18:2n6)	1105
mlon_1107	mlon	metabolomics	allantoin	1107
mlon_1110	mlon	metabolomics	arachidonate (20:4n6)	1110
mlon_1114	mlon	metabolomics	deoxycholate	1114
mlon_1118	mlon	metabolomics	arachidate (20:0)	1118
mlon_1121	mlon	metabolomics	margarate (17:0)	1121
mlon_1123	mlon	metabolomics	inosine	1123
mlon_1124	mlon	metabolomics	myo-inositol	1124
mlon_1125	mlon	metabolomics	isoleucine	1125
mlon_1126	mlon	metabolomics	alanine	1126
mlon_12017	mlon	metabolomics	3-methoxytyrosine	12017
mlon_12032	mlon	metabolomics	4-acetamidophenol	12032
mlon_12122	mlon	metabolomics	naproxen	12122
mlon_12129	mlon	metabolomics	beta-hydroxyisovalerate	12129
mlon_12261	mlon	metabolomics	taurodeoxycholate	12261
mlon_1284	mlon	metabolomics	threonine	1284
mlon_1299	mlon	metabolomics	tyrosine	1299
mlon_1301	mlon	metabolomics	lysine	1301
mlon_1302	mlon	metabolomics	methionine	1302
mlon_1303	mlon	metabolomics	malate	1303
mlon_1336	mlon	metabolomics	palmitate (16:0)	1336
mlon_1356	mlon	metabolomics	nonadecanoate (19:0)	1356
mlon_1358	mlon	metabolomics	stearate (18:0)	1358
mlon_1361	mlon	metabolomics	pentadecanoate (15:0)	1361
mlon_1365	mlon	metabolomics	myristate (14:0)	1365
mlon_1412	mlon	metabolomics	2′-deoxyuridine	1412
mlon_1414	mlon	metabolomics	3-phosphoglycerate	1414
mlon_1417	mlon	metabolomics	kynurenate	1417
mlon_1418	mlon	metabolomics	5,6-dihydrothymine	1418
mlon_1419	mlon	metabolomics	5-methylthioadenosine (MTA)	1419
mlon_1432	mlon	metabolomics	2-hydroxyphenylacetate	1432
mlon_1437	mlon	metabolomics	succinate	1437
mlon_1444	mlon	metabolomics	pipecolate	1444
mlon_1493	mlon	metabolomics	ornithine	1493
mlon_1494	mlon	metabolomics	5-oxoproline	1494
mlon_1496	mlon	metabolomics	methylmalonate (MMA)	1496
mlon_1498	mlon	metabolomics	N6,N6,N6-trimethyllysine	1498
mlon_1505	mlon	metabolomics	orotate	1505
mlon_1508	mlon	metabolomics	pantothenate (Vitamin B5)	1508
mlon_1512	mlon	metabolomics	picolinate	1512
mlon_15122	mlon	metabolomics	glycerol	15122
mlon_15136	mlon	metabolomics	xanthosine	15136
mlon_15140	mlon	metabolomics	kynurenine	15140
mlon_1515	mlon	metabolomics	salicylate	1515
mlon_1516	mlon	metabolomics	sarcosine	1516
mlon_1519	mlon	metabolomics	sucrose	1519
mlon_15336	mlon	metabolomics	tartarate	15336
mlon_15443	mlon	metabolomics	glucuronate	15443
mlon_1549	mlon	metabolomics	3-hydroxyisobutyrate	1549
mlon_15500	mlon	metabolomics	carnitine	15500
mlon_15506	mlon	metabolomics	choline	15506
mlon_1552	mlon	metabolomics	erucate (22:1n9)	1552
mlon_1558	mlon	metabolomics	4-acetamidobutanoate	1558
mlon_15581	mlon	metabolomics	xylose	15581
mlon_15586	mlon	metabolomics	maltose	15586
mlon_1561	mlon	metabolomics	alpha-tocopherol	1561
mlon_1563	mlon	metabolomics	chenodeoxycholate	1563
mlon_1564	mlon	metabolomics	citrate	1564
mlon_15650	mlon	metabolomics	1-methyladenosine	15650
mlon_1566	mlon	metabolomics	3-aminoisobutyrate	1566
mlon_15667	mlon	metabolomics	2-isopropylmalate	15667
mlon_1567	mlon	metabolomics	vanillylmandelate (VMA)	1567
mlon_15676	mlon	metabolomics	3-methyl-2-oxovalerate	15676
mlon_15677	mlon	metabolomics	3-methylhistidine	15677
mlon_15679	mlon	metabolomics	xanthurenate	15679
mlon_15681	mlon	metabolomics	4-guanidinobutanoate	15681
mlon_15685	mlon	metabolomics	5-hydroxylysine	15685
mlon_15705	mlon	metabolomics	cystathionine	15705
mlon_15716	mlon	metabolomics	imidazole lactate	15716
mlon_1572	mlon	metabolomics	glycerate	1572
mlon_15720	mlon	metabolomics	N-acetylglutamate	15720
mlon_15736	mlon	metabolomics	4-acetamidophenylglucuronide	15736
mlon_15745	mlon	metabolomics	methylsuccinate	15745
mlon_15749	mlon	metabolomics	3-phenylpropionate (hydrocinnamate)	15749
mlon_15753	mlon	metabolomics	hippurate	15753
mlon_15765	mlon	metabolomics	ethylmalonate	15765
mlon_15772	mlon	metabolomics	ribitol	15772
mlon_15778	mlon	metabolomics	benzoate	15778
mlon_1584	mlon	metabolomics	methyl indole-3-acetate	1584
mlon_1585	mlon	metabolomics	N-acetylalanine	1585
mlon_1587	mlon	metabolomics	N-acetylleucine	1587
mlon_1589	mlon	metabolomics	N-acetylmethionine	1589
mlon_1591	mlon	metabolomics	N-acetylvaline	1591
mlon_15958	mlon	metabolomics	phenylacetate	15958
mlon_15990	mlon	metabolomics	glycerophosphorylcholine (GPC)	15990
mlon_1600	mlon	metabolomics	phosphoethanolamine (PE)	1600
mlon_1604	mlon	metabolomics	urate	1604
mlon_1605	mlon	metabolomics	ursodeoxycholate	1605
mlon_1638	mlon	metabolomics	arginine	1638
mlon_1642	mlon	metabolomics	caprate (10:0)	1642
mlon_1643	mlon	metabolomics	fumarate	1643
mlon_1644	mlon	metabolomics	heptanoate (7:0)	1644
mlon_1645	mlon	metabolomics	laurate (12:0)	1645
mlon_1648	mlon	metabolomics	serine	1648
mlon_1649	mlon	metabolomics	valine	1649
mlon_1651	mlon	metabolomics	pyridoxal	1651
mlon_1669	mlon	metabolomics	4-hydroxyphenylpyruvate	1669
mlon_1670	mlon	metabolomics	urea	1670
mlon_1712	mlon	metabolomics	cortisol	1712
mlon_1769	mlon	metabolomics	cortisone	1769
mlon_17747	mlon	metabolomics	sphingosine	17747
mlon_17769	mlon	metabolomics	sphinganine	17769
mlon_17799	mlon	metabolomics	ibuprofen	17799
mlon_17805	mlon	metabolomics	dihomolinoleate (20:2n6)	17805
mlon_17945	mlon	metabolomics	2-hydroxystearate	17945
mlon_18037	mlon	metabolomics	metoprolol	18037
mlon_1806	mlon	metabolomics	retinol (Vitamin A)	1806
mlon_18245	mlon	metabolomics	gamma-glutamylhistidine	18245
mlon_18254	mlon	metabolomics	paraxanthine	18254
mlon_18280	mlon	metabolomics	gentisate	18280
mlon_18281	mlon	metabolomics	2-hydroxyhippurate (salicylurate)	18281
mlon_18335	mlon	metabolomics	quinate	18335
mlon_18349	mlon	metabolomics	indolelactate	18349
mlon_18362	mlon	metabolomics	azelate (nonanedioate; C9)	18362
mlon_18368	mlon	metabolomics	cys-gly, oxidized	18368
mlon_18369	mlon	metabolomics	gamma-glutamylleucine	18369
mlon_18374	mlon	metabolomics	methionine sulfoxide	18374
mlon_18392	mlon	metabolomics	theobromine	18392
mlon_18394	mlon	metabolomics	theophylline	18394
mlon_18467	mlon	metabolomics	eicosapentaenoate (EPA; 20:5n3)	18467
mlon_18474	mlon	metabolomics	estrone 3-sulfate	18474
mlon_18476	mlon	metabolomics	glycocholate	18476
mlon_18477	mlon	metabolomics	glycodeoxycholate	18477
mlon_18494	mlon	metabolomics	taurochenodeoxycholate	18494
mlon_18497	mlon	metabolomics	taurocholate	18497
mlon_1868	mlon	metabolomics	cysteine	1868
mlon_1898	mlon	metabolomics	proline	1898
mlon_1899	mlon	metabolomics	quinolinate	1899
mlon_19130	mlon	metabolomics	1,2-dipalmitoyl-GPC (16:0/16:0)	19130
mlon_19258	mlon	metabolomics	1-myristoyl-2-palmitoyl-GPC (14:0/16:0)	19258
mlon_19260	mlon	metabolomics	1-oleoyl-GPS (18:1)	19260
mlon_19263	mlon	metabolomics	1-palmitoyl-2-oleoyl-GPE (16:0/18:1)	19263
mlon_19265	mlon	metabolomics	1-stearoyl-2-oleoyl-GPS (18:0/18:1)	19265
mlon_19266	mlon	metabolomics	2-arachidonoylglycerol (20:4)	19266
mlon_19324	mlon	metabolomics	1-stearoyl-GPI (18:0)	19324
mlon_19503	mlon	metabolomics	stearoyl sphingomyelin (d18:1/18:0)	19503
mlon_20458	mlon	metabolomics	1-palmityl-GPC (O-16:0)	20458
mlon_20488	mlon	metabolomics	glucose	20488
mlon_20675	mlon	metabolomics	1,5-anhydroglucitol (1,5-AG)	20675
mlon_20676	mlon	metabolomics	maleate	20676
mlon_20693	mlon	metabolomics	tartronate (hydroxymalonate)	20693
mlon_20694	mlon	metabolomics	oxalate (ethanedioate)	20694
mlon_20699	mlon	metabolomics	erythritol	20699
mlon_21025	mlon	metabolomics	iminodiacetate (IDA)	21025
mlon_21049	mlon	metabolomics	1,6-anhydroglucose	21049
mlon_21127	mlon	metabolomics	1-palmitoylglycerol (16:0)	21127
mlon_21151	mlon	metabolomics	saccharin	21151
mlon_21158	mlon	metabolomics	3-hydroxymyristate	21158
mlon_21184	mlon	metabolomics	1-oleoylglycerol (18:1)	21184
mlon_21232	mlon	metabolomics	2-oleoylglycerol (18:1)	21232
mlon_2125	mlon	metabolomics	taurine	2125
mlon_2132	mlon	metabolomics	citrulline	2132
mlon_2137	mlon	metabolomics	biliverdin	2137
mlon_22001	mlon	metabolomics	3-hydroxyoctanoate	22001
mlon_22036	mlon	metabolomics	2-hydroxyoctanoate	22036
mlon_22053	mlon	metabolomics	3-hydroxydecanoate	22053
mlon_22116	mlon	metabolomics	4-methyl-2-oxopentanoate	22116
mlon_22130	mlon	metabolomics	phenyllactate (PLA)	22130
mlon_22132	mlon	metabolomics	alpha-hydroxyisocaproate	22132
mlon_22137	mlon	metabolomics	homoarginine	22137
mlon_22138	mlon	metabolomics	homocitrulline	22138
mlon_22154	mlon	metabolomics	bradykinin	22154
mlon_22163	mlon	metabolomics	EDTA	22163
mlon_22176	mlon	metabolomics	cysteine s-sulfate	22176
mlon_22185	mlon	metabolomics	N-acetylaspartate (NAA)	22185
mlon_22194	mlon	metabolomics	pyroglutamylglutamine	22194
mlon_22206	mlon	metabolomics	theanine	22206
mlon_22290	mlon	metabolomics	valproate (2-propylpentanoate)	22290
mlon_22842	mlon	metabolomics	cholate	22842
mlon_2342	mlon	metabolomics	serotonin	2342
mlon_2730	mlon	metabolomics	gamma-glutamylglutamine	2730
mlon_2734	mlon	metabolomics	gamma-glutamyltyrosine	2734
mlon_27414	mlon	metabolomics	beta-sitosterol	27414
mlon_27447	mlon	metabolomics	1-linoleoylglycerol (18:2)	27447
mlon_27513	mlon	metabolomics	indoleacetate	27513
mlon_2761	mlon	metabolomics	thyroxine	2761
mlon_27665	mlon	metabolomics	1-methylnicotinamide	27665
mlon_27672	mlon	metabolomics	3-indoxyl sulfate	27672
mlon_27710	mlon	metabolomics	N-acetylglycine	27710
mlon_27718	mlon	metabolomics	creatine	27718
mlon_27719	mlon	metabolomics	galactonate	27719
mlon_2772	mlon	metabolomics	topiramate	2772
mlon_27731	mlon	metabolomics	ribonate (ribonolactone)	27731
mlon_27738	mlon	metabolomics	threonate	27738
mlon_2829	mlon	metabolomics	N-formylmethionine	2829
mlon_30460	mlon	metabolomics	1-methylhistidine	30460
mlon_3127	mlon	metabolomics	hypoxanthine	3127
mlon_3141	mlon	metabolomics	betaine	3141
mlon_3147	mlon	metabolomics	xanthine	3147
mlon_31536	mlon	metabolomics	N-(2-furoyl)glycine	31536
mlon_31548	mlon	metabolomics	DSGEGDFXAEGGGVR*	31548
mlon_3155	mlon	metabolomics	3-ureidopropionate	3155
mlon_31555	mlon	metabolomics	pyridoxate	31555
mlon_31591	mlon	metabolomics	androsterone sulfate	31591
mlon_31787	mlon	metabolomics	3-carboxy-4-methyl-5-propyl-2-	31787
			furanpropanoate (CMPF)
mlon_31904	mlon	metabolomics	7-ketodeoxycholate	31904
mlon_31912	mlon	metabolomics	glycolithocholate	31912
mlon_31932	mlon	metabolomics	propionylglycine (C3)	31932
mlon_31934	mlon	metabolomics	2-hydroxyadipate	31934
mlon_31938	mlon	metabolomics	5-hydroxyhexanoate	31938
mlon_31943	mlon	metabolomics	3-hydroxysebacate	31943
mlon_32197	mlon	metabolomics	3-(4-hydroxyphenyl)lactate (HPLA)	32197
mlon_32198	mlon	metabolomics	acetylcarnitine (C2)	32198
mlon_32306	mlon	metabolomics	hydroxyproline	32306
mlon_32328	mlon	metabolomics	hexanoylcarnitine (C6)	32328
mlon_32342	mlon	metabolomics	AMP	32342
mlon_32346	mlon	metabolomics	glycochenodeoxycholate	32346
mlon_32350	mlon	metabolomics	1-methyl-4-imidazoleacetate	32350
mlon_32377	mlon	metabolomics	N-acetylneuraminate	32377
mlon_32388	mlon	metabolomics	dodecanedioate (C12)	32388
mlon_32390	mlon	metabolomics	N-acetyltyrosine	32390
mlon_32391	mlon	metabolomics	1,3-dimethylurate	32391
mlon_32394	mlon	metabolomics	pyroglutamylvaline	32394
mlon_32397	mlon	metabolomics	3-hydroxy-2-ethylpropionate	32397
mlon_32398	mlon	metabolomics	sebacate (C10-DC)	32398
mlon_32401	mlon	metabolomics	trigonelline (N′-methylnicotinate)	32401
mlon_32405	mlon	metabolomics	indolepropionate	32405
mlon_32412	mlon	metabolomics	butyrylcarnitine (C4)	32412
mlon_32415	mlon	metabolomics	docosadienoate (22:2n6)	32415
mlon_32417	mlon	metabolomics	docosatrienoate (22:3n3)	32417
mlon_32418	mlon	metabolomics	myristoleate (14:1n5)	32418
mlon_32425	mlon	metabolomics	dehydroisoandrosterone sulfate (DHEA-S)	32425
mlon_32426	mlon	metabolomics	I-urobilinogen	32426
mlon_32445	mlon	metabolomics	3-methylxanthine	32445
mlon_32452	mlon	metabolomics	propionylcarnitine (C3)	32452
mlon_32455	mlon	metabolomics	linoleamide (18:2n6)	32455
mlon_32457	mlon	metabolomics	3-hydroxylaurate	32457
mlon_32458	mlon	metabolomics	oleamide	32458
mlon_32462	mlon	metabolomics	N-linoleoylglycine	32462
mlon_32463	mlon	metabolomics	arachidonoyl ethanolamide	32463
mlon_32489	mlon	metabolomics	caproate (6:0)	32489
mlon_32492	mlon	metabolomics	caprylate (8:0)	32492
mlon_32497	mlon	metabolomics	10-undecenoate (11:1n1)	32497
mlon_32504	mlon	metabolomics	docosapentaenoate (DPA; 22:5n3)	32504
mlon_32506	mlon	metabolomics	2-linoleoylglycerol (18:2)	32506
mlon_32553	mlon	metabolomics	phenol sulfate	32553
mlon_32562	mlon	metabolomics	pregnen-diol disulfate*	32562
mlon_32586	mlon	metabolomics	bilirubin (E,E)*	32586
mlon_32599	mlon	metabolomics	glycocholenate sulfate*	32599
mlon_32619	mlon	metabolomics	pregnenediol sulfate (C21H34O5S)*	32619
mlon_32620	mlon	metabolomics	glycolithocholate sulfate*	32620
mlon_32807	mlon	metabolomics	taurocholenate sulfate*	32807
mlon_32815	mlon	metabolomics	2-arachidonoyl-GPE* (20:4)*	32815
mlon_32827	mlon	metabolomics	andro steroid monosulfate C19H28O6S (1)*	32827
mlon_32836	mlon	metabolomics	HWESASXX*	32836
mlon_32882	mlon	metabolomics	hydroxybupropion	32882
mlon_32980	mlon	metabolomics	adrenate (22:4n6)	32980
mlon_33009	mlon	metabolomics	homostachydrine*	33009
mlon_33161	mlon	metabolomics	2-methoxyacetaminophen glucuronide*	33161
mlon_33173	mlon	metabolomics	2-hydroxyacetaminophen sulfate*	33173
mlon_33228	mlon	metabolomics	1-arachidonoyl-GPC* (20:4)*	33228
mlon_33230	mlon	metabolomics	1-palmitoleoyl-GPC* (16:1)*	33230
mlon_33364	mlon	metabolomics	gamma-glutamylthreonine	33364
mlon_33384	mlon	metabolomics	salicyluric glucuronide*	33384
mlon_33387	mlon	metabolomics	2-arachidonoyl-GPC* (20:4)*	33387
mlon_33419	mlon	metabolomics	2-palmitoylglycerol (16:0)	33419
mlon_33422	mlon	metabolomics	gamma-glutamylphenylalanine	33422
mlon_33441	mlon	metabolomics	isobutyrylcarnitine (C4)	33441
mlon_33442	mlon	metabolomics	pseudouridine	33442
mlon_33447	mlon	metabolomics	palmitoleate (16:1n7)	33447
mlon_33587	mlon	metabolomics	eicosenoate (20:1n9 or 1n11)	33587
mlon_33821	mlon	metabolomics	1-eicosatrienoyl-GPC* (20:3)*	33821
mlon_33822	mlon	metabolomics	1-docosahexaenoyl-GPC* (22:6)*	33822
mlon_33871	mlon	metabolomics	1-eicosadienoyl-GPC* (20:2)*	33871
mlon_33934	mlon	metabolomics	gamma-glutamyl-epsilon-lysine	33934
mlon_33935	mlon	metabolomics	piperine	33935
mlon_33936	mlon	metabolomics	octanoylcarnitine (C8)	33936
mlon_33937	mlon	metabolomics	alpha-hydroxyisovalerate	33937
mlon_33939	mlon	metabolomics	N-acetylthreonine	33939
mlon_33941	mlon	metabolomics	decanoylcarnitine (C10)	33941
mlon_33943	mlon	metabolomics	N-acetylglutamine	33943
mlon_33946	mlon	metabolomics	N-acetylhistidine	33946
mlon_33947	mlon	metabolomics	gamma-glutamyltryptophan	33947
mlon_33949	mlon	metabolomics	gamma-glutamylglycine	33949
mlon_33950	mlon	metabolomics	N-acetylphenylalanine	33950
mlon_33952	mlon	metabolomics	myristoylcarnitine (C14)	33952
mlon_33953	mlon	metabolomics	N-acetylarginine	33953
mlon_33955	mlon	metabolomics	1-palmitoyl-GPC (16:0)	33955
mlon_33959	mlon	metabolomics	N-acetyltryptophan	33959
mlon_33961	mlon	metabolomics	1-stearoyl-GPC (18:0)	33961
mlon_33962	mlon	metabolomics	(Hyp-3)-Bradykinin	33962
mlon_33967	mlon	metabolomics	N-acetylisoleucine	33967
mlon_33968	mlon	metabolomics	5-dodecenoate (12:1n7)	33968
mlon_33969	mlon	metabolomics	stearidonate (18:4n3)	33969
mlon_33971	mlon	metabolomics	10-heptadecenoate (17:1n7)	33971
mlon_33972	mlon	metabolomics	10-nonadecenoate (19:1n9)	33972
mlon_33973	mlon	metabolomics	epiandrosterone sulfate	33973
mlon_33983	mlon	metabolomics	tauro-beta-muricholate	33983
mlon_33997	mlon	metabolomics	campesterol	33997
mlon_34035	mlon	metabolomics	linolenate (18:3n3 or 3n6)	34035
mlon_34093	mlon	metabolomics	hyocholate	34093
mlon_34109	mlon	metabolomics	metoprolol acid metabolite*	34109
mlon_34214	mlon	metabolomics	1-arachidonoyl-GPI* (20:4)*	34214
mlon_34258	mlon	metabolomics	2-docosahexaenoyl-GPE (22:6)*	34258
mlon_34365	mlon	metabolomics	3-(cystein-S-yl)acetaminophen*	34365
mlon_34384	mlon	metabolomics	stachydrine	34384
mlon_34387	mlon	metabolomics	N-acetylproline	34387
mlon_34389	mlon	metabolomics	1-methylxanthine	34389
mlon_34390	mlon	metabolomics	7-methylxanthine	34390
mlon_34393	mlon	metabolomics	1-linolenoylglycerol (18:3)	34393
mlon_34395	mlon	metabolomics	1-methylurate	34395
mlon_34396	mlon	metabolomics	phosphocholine	34396
mlon_34397	mlon	metabolomics	1-arachidonylglycerol (20:4)	34397
mlon_34399	mlon	metabolomics	3,7-dimethylurate	34399
mlon_34400	mlon	metabolomics	1,7-dimethylurate	34400
mlon_34401	mlon	metabolomics	5-acetylamino-6-formylamino-3-methyluracil	34401
mlon_34404	mlon	metabolomics	1,3,7-trimethylurate	34404
mlon_34407	mlon	metabolomics	isovalerylcarnitine (C5)	34407
mlon_34409	mlon	metabolomics	stearoylcarnitine (C18)	34409
mlon_34419	mlon	metabolomics	1-linoleoyl-GPC (18:2)	34419
mlon_34420	mlon	metabolomics	bradykinin, des-arg(9)	34420
mlon_34424	mlon	metabolomics	5-acetylamino-6-amino-3-methyluracil	34424
mlon_34437	mlon	metabolomics	1-stearoyl-GPG (18:0)	34437
mlon_34445	mlon	metabolomics	sphingosine 1-phosphate	34445
mlon_34456	mlon	metabolomics	gamma-glutamylisoleucine*	34456
mlon_34534	mlon	metabolomics	laurylcarnitine (C12)	34534
mlon_34565	mlon	metabolomics	1-palmitoleoyl-GPE (16:1)*	34565
mlon_35107	mlon	metabolomics	isovalerylglycine	35107
mlon_35114	mlon	metabolomics	7-methylguanine	35114
mlon_35126	mlon	metabolomics	phenylacetylglutamine	35126
mlon_35127	mlon	metabolomics	prolylhydroxyproline	35127
mlon_35130	mlon	metabolomics	N4-acetylcytidine	35130
mlon_35136	mlon	metabolomics	5-methyluridine (ribothymidine)	35136
mlon_35137	mlon	metabolomics	N2,N2-dimethylguanosine	35137
mlon_35153	mlon	metabolomics	1-docosahexaenoylglycerol (22:6)	35153
mlon_35157	mlon	metabolomics	N6-carbamoylthreonyladenosine	35157
mlon_35159	mlon	metabolomics	cysteine-glutathione disulfide	35159
mlon_35160	mlon	metabolomics	oleoylcarnitine (C18)	35160
mlon_35172	mlon	metabolomics	orotidine	35172
mlon_35186	mlon	metabolomics	1-arachidonoyl-GPE (20:4n6)*	35186
mlon_35253	mlon	metabolomics	2-palmitoyl-GPC* (16:0)*	35253
mlon_35257	mlon	metabolomics	2-linoleoyl-GPC* (18:2)*	35257
mlon_35305	mlon	metabolomics	1-palmitoyl-GPI* (16:0)	35305
mlon_35320	mlon	metabolomics	catechol sulfate	35320
mlon_35322	mlon	metabolomics	hydroquinone sulfate	35322
mlon_35428	mlon	metabolomics	tiglyl carnitine (C5)	35428
mlon_35436	mlon	metabolomics	hexanoylglycine (C6)	35436
mlon_35437	mlon	metabolomics	isobutyrylglycine (C4)	35437
mlon_35527	mlon	metabolomics	4-hydroxyhippurate	35527
mlon_35625	mlon	metabolomics	1-myristoylglycerol (14:0)	35625
mlon_35626	mlon	metabolomics	2-myristoyl-GPC* (14:0)*	35626
mlon_35628	mlon	metabolomics	1-oleoyl-GPE (18:1)	35628
mlon_35631	mlon	metabolomics	1-palmitoyl-GPE (16:0)	35631
mlon_35635	mlon	metabolomics	3-(3-hydroxyphenyl)propionate	35635
mlon_35637	mlon	metabolomics	cysteinylglycine	35637
mlon_35651	mlon	metabolomics	ectoine	35651
mlon_35665	mlon	metabolomics	N-acetyl-aspartyl-glutamate (NAAG)	35665
mlon_35669	mlon	metabolomics	tetradecanedioate (C14)	35669
mlon_35675	mlon	metabolomics	2-hydroxypalmitate	35675
mlon_35678	mlon	metabolomics	hexadecanedioate (C16)	35678
mlon_35718	mlon	metabolomics	dihomolinolenate (20:3n3 or 3n6)	35718
mlon_36095	mlon	metabolomics	thymol sulfate	36095
mlon_36098	mlon	metabolomics	4-vinylphenol sulfate	36098
mlon_36099	mlon	metabolomics	4-ethylphenyl sulfate	36099
mlon_36103	mlon	metabolomics	p-cresol sulfate	36103
mlon_36593	mlon	metabolomics	2-linoleoyl-GPE* (18:2)*	36593
mlon_36594	mlon	metabolomics	1-linoleoyl-GPI* (18:2)*	36594
mlon_36600	mlon	metabolomics	1-linoleoyl-GPE (18:2)*	36600
mlon_36602	mlon	metabolomics	1-oleoyl-GPI (18:1)*	36602
mlon_36618	mlon	metabolomics	1-palmitoleoyl-GPI* (16:1)*	36618
mlon_36649	mlon	metabolomics	sucralose	36649
mlon_36713	mlon	metabolomics	N6-carboxymethyllysine	36713
mlon_36738	mlon	metabolomics	gamma-glutamylglutamate	36738
mlon_36746	mlon	metabolomics	2-hydroxy-3-methylvalerate	36746
mlon_36747	mlon	metabolomics	deoxycarnitine	36747
mlon_36751	mlon	metabolomics	N2-acetyllysine	36751
mlon_36752	mlon	metabolomics	N6-acetyllysine	36752
mlon_36754	mlon	metabolomics	octadecanedioate (C18)	36754
mlon_36776	mlon	metabolomics	7-HOCA	36776
mlon_36808	mlon	metabolomics	dimethylarginine (ADMA + SDMA)	36808
mlon_36845	mlon	metabolomics	o-cresol sulfate	36845
mlon_36850	mlon	metabolomics	taurolithocholate 3-sulfate	36850
mlon_37020	mlon	metabolomics	carbamazepine 10,11-epoxide*	37020
mlon_37033	mlon	metabolomics	carbamazepine	37033
mlon_37058	mlon	metabolomics	succinylcarnitine (C4)	37058
mlon_37059	mlon	metabolomics	malonylcarnitine	37059
mlon_37063	mlon	metabolomics	gamma-glutamylalanine	37063
mlon_37073	mlon	metabolomics	alpha-hydroxycaproate	37073
mlon_37076	mlon	metabolomics	N-acetylserine	37076
mlon_37097	mlon	metabolomics	tryptophan betaine	37097
mlon_37112	mlon	metabolomics	chiro-inositol	37112
mlon_37174	mlon	metabolomics	21-hydroxypregnenolone monosulfate (1)	37174
mlon_37181	mlon	metabolomics	4-allylphenol sulfate	37181
mlon_37183	mlon	metabolomics	5alpha-androstan-3alpha,17alpha-diol monosulfate	37183
mlon_37184	mlon	metabolomics	5alpha-androstan-3alpha,17beta-diol disulfate	37184
mlon_37185	mlon	metabolomics	5alpha-androstan-3alpha,17beta-diol monosulfate (2)	37185
mlon_37186	mlon	metabolomics	5alpha-androstan-3alpha,17beta-diol monosulfate (1)	37186
mlon_37187	mlon	metabolomics	5alpha-androstan-3beta,17alpha-diol disulfate	37187
mlon_37190	mlon	metabolomics	5alpha-androstan-3beta,17beta-diol disulfate	37190
mlon_37192	mlon	metabolomics	5alpha-androstan-3beta,17beta-diol monosulfate (2)	37192
mlon_37196	mlon	metabolomics	5alpha-pregnan-3beta,20beta-diol monosulfate (1)	37196
mlon_37198	mlon	metabolomics	5alpha-pregnan-3beta,20alpha-diol disulfate	37198
mlon_37200	mlon	metabolomics	5alpha-pregnan-3beta,20alpha-diol monosulfate (2)	37200
mlon_37202	mlon	metabolomics	androstenediol (3beta,17beta) disulfate (1)	37202
mlon_37203	mlon	metabolomics	androstenediol (3beta,17beta) disulfate (2)	37203
mlon_37207	mlon	metabolomics	androstenediol (3alpha,17alpha) monosulfate (2)	37207
mlon_37209	mlon	metabolomics	androstenediol (3alpha,17alpha) monosulfate (3)	37209
mlon_37210	mlon	metabolomics	androstenediol (3beta,17beta) monosulfate (2)	37210
mlon_37211	mlon	metabolomics	androstenediol (3beta,17beta) monosulfate (1)	37211
mlon_37231	mlon	metabolomics	1-docosapentaenoyl-GPC* (22:5n3)*	37231
mlon_37418	mlon	metabolomics	1-pentadecanoyl-GPC (15:0)*	37418
mlon_37419	mlon	metabolomics	1-margaroyl-GPE (17:0)*	37419
mlon_37431	mlon	metabolomics	N-methylproline	37431
mlon_37432	mlon	metabolomics	N-acetyl-beta-alanine	37432
mlon_37443	mlon	metabolomics	cysteine sulfinic acid	37443
mlon_37445	mlon	metabolomics	4-hydroxycoumarin	37445
mlon_37455	mlon	metabolomics	glycerophosphoethanolamine	37455
mlon_37459	mlon	metabolomics	ergothioneine	37459
mlon_37475	mlon	metabolomics	4-acetaminophen sulfate	37475
mlon_37478	mlon	metabolomics	docosapentaenoate (n6 DPA; 22:5n6)	37478
mlon_37480	mlon	metabolomics	5alpha-pregnan-3beta-ol,20-one sulfate	37480
mlon_37482	mlon	metabolomics	17alpha-hydroxypregnenolone 3-sulfate	37482
mlon_37496	mlon	metabolomics	N-acetylputrescine	37496
mlon_37506	mlon	metabolomics	palmitoyl sphingomyelin (d18:1/16:0)	37506
mlon_37529	mlon	metabolomics	sphingomyelin (d18:1/18:1, d18:2/18:0)	37529
mlon_37536	mlon	metabolomics	12-HETE	37536
mlon_37538	mlon	metabolomics	15-HETE	37538
mlon_37752	mlon	metabolomics	13-HODE + 9-HODE	37752
mlon_38102	mlon	metabolomics	oleoyl ethanolamide	38102
mlon_38116	mlon	metabolomics	indole-3-carboxylate	38116
mlon_38125	mlon	metabolomics	4-cholesten-3-one	38125
mlon_38127	mlon	metabolomics	S-methylmethionine	38127
mlon_38165	mlon	metabolomics	palmitoyl ethanolamide	38165
mlon_38168	mlon	metabolomics	16a-hydroxy DHEA 3-sulfate	38168
mlon_38170	mlon	metabolomics	pregnenolone sulfate	38170
mlon_38178	mlon	metabolomics	cis-4-decenoylcarnitine (C10:1)	38178
mlon_38276	mlon	metabolomics	2,3-dihydroxyisovalerate	38276
mlon_38293	mlon	metabolomics	(12 or 13)-methylmyristate (a15:0 or i15:0)	38293
mlon_38296	mlon	metabolomics	(16 or 17)-methylstearate (a19:0 or i19:0)	38296
mlon_38306	mlon	metabolomics	metformin	38306
mlon_38309	mlon	metabolomics	4-hydroxynonenal	38309
mlon_38321	mlon	metabolomics	allopurinol riboside	38321
mlon_38366	mlon	metabolomics	ibuprofen acyl glucuronide	38366
mlon_38395	mlon	metabolomics	12,13-DiHOME	38395
mlon_38399	mlon	metabolomics	9,10-DiHOME	38399
mlon_38595	mlon	metabolomics	ranitidine	38595
mlon_38599	mlon	metabolomics	celecoxib	38599
mlon_38600	mlon	metabolomics	omeprazole	38600
mlon_38609	mlon	metabolomics	pantoprazole	38609
mlon_38623	mlon	metabolomics	venlafaxine	38623
mlon_38637	mlon	metabolomics	cinnamoylglycine	38637
mlon_38658	mlon	metabolomics	atenolol	38658
mlon_38661	mlon	metabolomics	hydroxycotinine	38661
mlon_38662	mlon	metabolomics	cotinine N-oxide	38662
mlon_38667	mlon	metabolomics	3-methylglutaconate	38667
mlon_38669	mlon	metabolomics	diphenhydramine	38669
mlon_38686	mlon	metabolomics	gabapentin	38686
mlon_38768	mlon	metabolomics	(14 or 15)-methylpalmitate (a17:0 or i17:0)	38768
mlon_39221	mlon	metabolomics	2-linoleoyl-GPI (18:2)*	39221
mlon_39223	mlon	metabolomics	2-stearoyl-GPI (18:0)*	39223
mlon_39270	mlon	metabolomics	1-(1-enyl-palmitoyl)-GPE (P-16:0)*	39270
mlon_39271	mlon	metabolomics	1-(1-enyl-stearoyl)-GPE (P-18:0)*	39271
mlon_39273	mlon	metabolomics	doxycycline	39273
mlon_39346	mlon	metabolomics	alpha-CEHC glucuronide*	39346
mlon_39378	mlon	metabolomics	tauroursodeoxycholate	39378
mlon_39379	mlon	metabolomics	glycoursodeoxycholate	39379
mlon_39586	mlon	metabolomics	pseudoephedrine	39586
mlon_39592	mlon	metabolomics	S-methylcysteine	39592
mlon_39598	mlon	metabolomics	7-methylurate	39598
mlon_396	mlon	metabolomics	glutarate (C5-DC)	396
mlon_39600	mlon	metabolomics	3-hydroxyhippurate	39600
mlon_39603	mlon	metabolomics	ethyl glucuronide	39603
mlon_39609	mlon	metabolomics	16-hydroxypalmitate	39609
mlon_39625	mlon	metabolomics	hydrochlorothiazide	39625
mlon_39730	mlon	metabolomics	N-stearoyltaurine	39730
mlon_39732	mlon	metabolomics	N-oleoyltaurine	39732
mlon_39757	mlon	metabolomics	sertraline	39757
mlon_39767	mlon	metabolomics	quinine	39767
mlon_39787	mlon	metabolomics	quetiapine	39787
mlon_39788	mlon	metabolomics	solanidine	39788
mlon_39792	mlon	metabolomics	1-behenoyl-GPC (22:0)	39792
mlon_39831	mlon	metabolomics	eicosanodioate (C20-DC)	39831
mlon_39835	mlon	metabolomics	N-palmitoyltaurine	39835
mlon_39837	mlon	metabolomics	docosadioate (C22-DC)	39837
mlon_39994	mlon	metabolomics	valylleucine	39994
mlon_40007	mlon	metabolomics	carboxyethyl-GABA	40007
mlon_40062	mlon	metabolomics	4-hydroxy-2-oxoglutaric acid	40062
mlon_40173	mlon	metabolomics	L-urobilin	40173
mlon_40406	mlon	metabolomics	trimethylamine N-oxide	40406
mlon_40450	mlon	metabolomics	duloxetine	40450
mlon_40456	mlon	metabolomics	fluvoxamine	40456
mlon_40459	mlon	metabolomics	escitalopram	40459
mlon_40461	mlon	metabolomics	paroxetine	40461
mlon_40469	mlon	metabolomics	N1-Methyl-2-pyridone-5-carboxamide	40469
mlon_40473	mlon	metabolomics	hydantoin-5-propionate	40473
mlon_40481	mlon	metabolomics	dihydroferulic acid	40481
mlon_40499	mlon	metabolomics	4-hydroxyglutamate	40499
mlon_40685	mlon	metabolomics	methionylalanine	40685
mlon_40703	mlon	metabolomics	prolylglycine	40703
mlon_40708	mlon	metabolomics	pregnanediol-3-glucuronide	40708
mlon_40730	mlon	metabolomics	imidazole propionate	40730
mlon_41220	mlon	metabolomics	2-stearoyl-GPE (18:0)*	41220
mlon_41377	mlon	metabolomics	phenylalanyltryptophan	41377
mlon_41494	mlon	metabolomics	alliin	41494
mlon_41754	mlon	metabolomics	heme	41754
mlon_41888	mlon	metabolomics	succinimide	41888
mlon_42002	mlon	metabolomics	lanthionine	42002
mlon_42021	mlon	metabolomics	fexofenadine	42021
mlon_42027	mlon	metabolomics	histidylalanine	42027
mlon_42077	mlon	metabolomics	seryltyrosine	42077
mlon_42087	mlon	metabolomics	indoleacetylglutamine	42087
mlon_42092	mlon	metabolomics	N-palmitoylglycine	42092
mlon_42095	mlon	metabolomics	palmitamide (16:0)	42095
mlon_42109	mlon	metabolomics	phosphate	42109
mlon_42370	mlon	metabolomics	S-1-pyrroline-5-carboxylate	42370
mlon_42374	mlon	metabolomics	2-aminobutyrate	42374
mlon_42381	mlon	metabolomics	gamma-CEHC glucuronide*	42381
mlon_42382	mlon	metabolomics	S-adenosylhomocysteine (SAH)	42382
mlon_42398	mlon	metabolomics	1-stearoyl-GPE (18:0)	42398
mlon_42420	mlon	metabolomics	erythronate*	42420
mlon_42446	mlon	metabolomics	1-palmitoyl-2-linoleoyl-GPC (16:0/18:2)	42446
mlon_42448	mlon	metabolomics	1-stearoyl-2-oleoyl-GPE (18:0/18:1)	42448
mlon_42449	mlon	metabolomics	1-palmitoyl-2-linoleoyl-GPE (16:0/18:2)	42449
mlon_42450	mlon	metabolomics	1-stearoyl-2-arachidonoyl-GPC (18:0/20:4)	42450
mlon_42459	mlon	metabolomics	sphingomyelin (d18:2/16:0, d18:1/16:1)*	42459
mlon_42463	mlon	metabolomics	sphingomyelin (d18:1/14:0, d16:1/16:0)*	42463
mlon_42489	mlon	metabolomics	2-hydroxydecanoate	42489
mlon_42574	mlon	metabolomics	glycohyocholate	42574
mlon_42613	mlon	metabolomics	famotidine	42613
mlon_42989	mlon	metabolomics	N-methyltaurine	42989
mlon_43231	mlon	metabolomics	6-oxopiperidine-2-carboxylate	43231
mlon_43239	mlon	metabolomics	S-allylcysteine	43239
mlon_43249	mlon	metabolomics	N-delta-acetylornithine	43249
mlon_43255	mlon	metabolomics	N-acetyl-1-methylhistidine*	43255
mlon_43256	mlon	metabolomics	N-acetyl-3-methylhistidine*	43256
mlon_43258	mlon	metabolomics	acisoga	43258
mlon_43264	mlon	metabolomics	3-hydroxybutyrylcarnitine (1)	43264
mlon_43265	mlon	metabolomics	benzoylcarnitine*	43265
mlon_43266	mlon	metabolomics	2-aminophenol sulfate	43266
mlon_43330	mlon	metabolomics	2-hydroxyibuprofen	43330
mlon_43333	mlon	metabolomics	carboxyibuprofen	43333
mlon_43334	mlon	metabolomics	O-desmethylvenlafaxine	43334
mlon_43335	mlon	metabolomics	warfarin	43335
mlon_43343	mlon	metabolomics	2-aminooctanoate	43343
mlon_43374	mlon	metabolomics	indolin-2-one	43374
mlon_43378	mlon	metabolomics	S-methylcysteine sulfoxide	43378
mlon_43400	mlon	metabolomics	2-piperidinone	43400
mlon_43424	mlon	metabolomics	dimethyl sulfone	43424
mlon_43488	mlon	metabolomics	N-acetylcarnosine	43488
mlon_43493	mlon	metabolomics	formiminoglutamate	43493
mlon_43496	mlon	metabolomics	3-hydroxyquinine	43496
mlon_43507	mlon	metabolomics	3b-hydroxy-5-cholenoic acid	43507
mlon_43530	mlon	metabolomics	N-acetyl-cadaverine	43530
mlon_43534	mlon	metabolomics	allopurinol	43534
mlon_43582	mlon	metabolomics	5-(galactosylhydroxy)-L-lysine	43582
mlon_43591	mlon	metabolomics	N2,N5-diacetylornithine	43591
mlon_43592	mlon	metabolomics	4-methylbenzenesulfonate	43592
mlon_43761	mlon	metabolomics	2-aminoheptanoate	43761
mlon_43802	mlon	metabolomics	guanidinoacetate	43802
mlon_43807	mlon	metabolomics	bilirubin	43807
mlon_43829	mlon	metabolomics	gamma-glutamylvaline	43829
mlon_43847	mlon	metabolomics	glycerol 3-phosphate	43847
mlon_443	mlon	metabolomics	aspartate	443
mlon_44526	mlon	metabolomics	3-methyl-2-oxobutyrate	44526
mlon_44560	mlon	metabolomics	1-eicosenoyl-GPC (20:1)*	44560
mlon_44563	mlon	metabolomics	1-eicosapentaenoyl-GPC (20:5)*	44563
mlon_44618	mlon	metabolomics	3-methoxytyramine sulfate	44618
mlon_44620	mlon	metabolomics	4-acetylphenyl sulfate	44620
mlon_44621	mlon	metabolomics	1-(1-enyl-oleoyl)-GPE (P-18:1)*	44621
mlon_44630	mlon	metabolomics	1-dihomo-linolenoyl-GPE (20:3n3 or 6)*	44630
mlon_44633	mlon	metabolomics	1-docosahexaenoyl-GPE (22:6)*	44633
mlon_44656	mlon	metabolomics	isovalerate (C5)	44656
mlon_44657	mlon	metabolomics	HWESASLLR	44657
mlon_44664	mlon	metabolomics	glutaroylcarnitine (C5)	44664
mlon_44675	mlon	metabolomics	docosahexaenoate (DHA; 22:6n3)	44675
mlon_44681	mlon	metabolomics	palmitoylcarnitine (C16)	44681
mlon_44682	mlon	metabolomics	1-heptadecanoyl-GPC (17:0)	44682
mlon_44683	mlon	metabolomics	2-margaroyl-GPC (17:0)*	44683
mlon_44688	mlon	metabolomics	maltotriose	44688
mlon_44872	mlon	metabolomics	gamma-glutamylmethionine	44872
mlon_44876	mlon	metabolomics	gamma-CEHC	44876
mlon_44877	mlon	metabolomics	N-palmitoyl-sphingosine (d18:1/16:0)	44877
mlon_44878	mlon	metabolomics	methionine sulfone	44878
mlon_45095	mlon	metabolomics	2-methylbutyroylcarnitine (C5)	45095
mlon_45404	mlon	metabolomics	N-acetylalliin	45404
mlon_45413	mlon	metabolomics	O-sulfo-L-tyrosine	45413
mlon_45415	mlon	metabolomics	3-(3-hydroxyphenyl)propionate sulfate	45415
mlon_45452	mlon	metabolomics	2-palmitoyl-GPE* (16:0)*	45452
mlon_45453	mlon	metabolomics	1-myristoyl-GPC (14:0)	45453
mlon_45455	mlon	metabolomics	2-oleoyl-GPE* (18:1)*	45455
mlon_45456	mlon	metabolomics	1-arachidoyl-GPC (20:0)	45456
mlon_45675	mlon	metabolomics	1-docosapentaenoyl-GPC* (22:5n6)*	45675
mlon_45721	mlon	metabolomics	3-(N-acetyl-L-cystein-S-yl) acetaminophen	45721
mlon_45951	mlon	metabolomics	1-linolenoyl-GPC (18:3)*	45951
mlon_45966	mlon	metabolomics	1-stearoyl-GPS (18:0)*	45966
mlon_45968	mlon	metabolomics	1-oleoyl-GPG (18:1)*	45968
mlon_45970	mlon	metabolomics	1-palmitoyl-GPG (16:0)*	45970
mlon_46106	mlon	metabolomics	desmethylnaproxen sulfate	46106
mlon_46111	mlon	metabolomics	guaiacol sulfate	46111
mlon_46115	mlon	metabolomics	21-hydroxypregnenolone disulfate	46115
mlon_46142	mlon	metabolomics	mannitol/sorbitol	46142
mlon_46144	mlon	metabolomics	methyl glucopyranoside (alpha + beta)	46144
mlon_46146	mlon	metabolomics	4-methylcatechol sulfate	46146
mlon_46164	mlon	metabolomics	3-methyl catechol sulfate (2)	46164
mlon_46165	mlon	metabolomics	3-methyl catechol sulfate (1)	46165
mlon_46172	mlon	metabolomics	5alpha-pregnan-diol disulfate	46172
mlon_46173	mlon	metabolomics	aconitate [cis or trans]	46173
mlon_46203	mlon	metabolomics	2-docosahexaenoyl-GPC* (22:6)*	46203
mlon_46223	mlon	metabolomics	linoleoylcarnitine (C18:2)*	46223
mlon_46225	mlon	metabolomics	pyroglutamine*	46225
mlon_46301	mlon	metabolomics	9-HETE	46301
mlon_46331	mlon	metabolomics	desmethylnaproxen	46331
mlon_46342	mlon	metabolomics	leukotriene B5	46342
mlon_46539	mlon	metabolomics	N-acetylglucosamine/N-acetylgalactosamine	46539
mlon_46548	mlon	metabolomics	3-methylglutarylcarnitine (2)	46548
mlon_46798	mlon	metabolomics	oleoyl-linoleoyl-glycerol (18:1/18:2) [1]	46798
mlon_46799	mlon	metabolomics	oleoyl-linoleoyl-glycerol (18:1/18:2) [2]	46799
mlon_46957	mlon	metabolomics	gulonate*	46957
mlon_46960	mlon	metabolomics	sulfate*	46960
mlon_47031	mlon	metabolomics	2-methoxyacetaminophen sulfate*	47031
mlon_47101	mlon	metabolomics	N-methylpipecolate	47101
mlon_47112	mlon	metabolomics	etiocholanolone glucuronide	47112
mlon_47114	mlon	metabolomics	ferulic acid 4-sulfate	47114
mlon_47118	mlon	metabolomics	2-palmitoleoyl-GPC* (16:1)*	47118
mlon_47120	mlon	metabolomics	9-hydroxystearate	47120
mlon_47132	mlon	metabolomics	5alpha-androstan-3alpha,17beta-diol 17-	47132
			glucuronide
mlon_47136	mlon	metabolomics	N-acetyl-S-allyl-L-cysteine	47136
mlon_47153	mlon	metabolomics	sphingomyelin (d18:1/24:1, d18:2/24:0)*	47153
mlon_47154	mlon	metabolomics	sphingomyelin (d18:2/14:0, d18:1/14:1)*	47154
mlon_47403	mlon	metabolomics	17alpha-hydroxypregnanolone glucuronide	47403
mlon_47666	mlon	metabolomics	alpha-CEHC sulfate	47666
mlon_47886	mlon	metabolomics	bilirubin (E,Z or Z,E)*	47886
mlon_47888	mlon	metabolomics	1-eicosapentaenoyl-GPE (20:5)*	47888
mlon_47898	mlon	metabolomics	1-pentadecanoylglycerol (15:0)	47898
mlon_48143	mlon	metabolomics	2-propyl-4-pentenoate (4-ene-valproate)	48143
mlon_48153	mlon	metabolomics	mannose	48153
mlon_48182	mlon	metabolomics	myristoleoylcarnitine (C14:1)*	48182
mlon_48187	mlon	metabolomics	N-acetyltaurine	48187
mlon_48188	mlon	metabolomics	alpha-CEHC	48188
mlon_48195	mlon	metabolomics	fructose	48195
mlon_48255	mlon	metabolomics	arabonate/xylonate	48255
mlon_48258	mlon	metabolomics	1-oleoyl-GPC (18:1)	48258
mlon_48259	mlon	metabolomics	2-oleoyl-GPC* (18:1)*	48259
mlon_48341	mlon	metabolomics	1-dihomo-linolenylglycerol (20:3)	48341
mlon_48351	mlon	metabolomics	N1-methylinosine	48351
mlon_48394	mlon	metabolomics	pregnanolone/allopregnanolone sulfate	48394
mlon_48406	mlon	metabolomics	dopamine 4-sulfate	48406
mlon_48407	mlon	metabolomics	dopamine 3-O-sulfate	48407
mlon_48408	mlon	metabolomics	tyramine O-sulfate	48408
mlon_48425	mlon	metabolomics	phenylacetylcarnitine	48425
mlon_48428	mlon	metabolomics	pyrraline	48428
mlon_48429	mlon	metabolomics	methyl-4-hydroxybenzoate sulfate	48429
mlon_48433	mlon	metabolomics	N-formylphenylalanine	48433
mlon_48434	mlon	metabolomics	N-acetylcitrulline	48434
mlon_48441	mlon	metabolomics	4-hydroxychlorothalonil	48441
mlon_48442	mlon	metabolomics	4-vinylguaiacol sulfate	48442
mlon_48445	mlon	metabolomics	2-methoxyresorcinol sulfate	48445
mlon_48448	mlon	metabolomics	3-hydroxypyridine sulfate	48448
mlon_48460	mlon	metabolomics	propyl 4-hydroxybenzoate sulfate	48460
mlon_48490	mlon	metabolomics	sphingomyelin (d18:1/20:0, d16:1/22:0)*	48490
mlon_48491	mlon	metabolomics	sphingomyelin (d18:1/20:1, d18:2/20:0)*	48491
mlon_48492	mlon	metabolomics	behenoyl sphingomyelin (d18:1/22:0)*	48492
mlon_48493	mlon	metabolomics	sphingomyelin (d18:1/22:1, d18:2/22:0, d16:1/24:1)*	48493
mlon_485	mlon	metabolomics	spermidine	485
mlon_48566	mlon	metabolomics	valsartan	48566
mlon_48569	mlon	metabolomics	acesulfame	48569
mlon_48580	mlon	metabolomics	2-acetamidophenol sulfate	48580
mlon_48674	mlon	metabolomics	umbelliferone sulfate	48674
mlon_48693	mlon	metabolomics	3-acetylphenol sulfate	48693
mlon_48698	mlon	metabolomics	6-hydroxyindole sulfate	48698
mlon_48715	mlon	metabolomics	eugenol sulfate	48715
mlon_48728	mlon	metabolomics	daidzein sulfate (2)	48728
mlon_48733	mlon	metabolomics	vanillic alcohol sulfate	48733
mlon_48757	mlon	metabolomics	N-acetylkynurenine (2)	48757
mlon_48761	mlon	metabolomics	1,2,3-benzenetriol sulfate (1)	48761
mlon_48762	mlon	metabolomics	1,2,3-benzenetriol sulfate (2)	48762
mlon_48763	mlon	metabolomics	3-methoxycatechol sulfate (1)	48763
mlon_48782	mlon	metabolomics	C-glycosyltryptophan	48782
mlon_48841	mlon	metabolomics	p-cresol glucuronide*	48841
mlon_48857	mlon	metabolomics	glycerophosphoglycerol	48857
mlon_48885	mlon	metabolomics	arabitol/xylitol	48885
mlon_48990	mlon	metabolomics	pyruvate	48990
mlon_48997	mlon	metabolomics	isoeugenol sulfate	48997
mlon_49617	mlon	metabolomics	1-lignoceroyl-GPC (24:0)	49617
mlon_4968	mlon	metabolomics	alpha-ketobutyrate	4968
mlon_5086	mlon	metabolomics	dimethylglycine	5086
mlon_512	mlon	metabolomics	asparagine	512
mlon_513	mlon	metabolomics	creatinine	513
mlon_514	mlon	metabolomics	cytidine	514
mlon_52234	mlon	metabolomics	glycosyl-N-stearoyl-sphingosine (d18:1/18:0)	52234
mlon_52235	mlon	metabolomics	1-stearoyl-2-arachidonoyl-GPS (18:0/20:4)	52235
mlon_52281	mlon	metabolomics	2-hydroxybutyrate/2-hydroxyisobutyrate	52281
mlon_52285	mlon	metabolomics	oleate/vaccenate (18:1)	52285
mlon_52294	mlon	metabolomics	2-hydroxyglutarate	52294
mlon_52322	mlon	metabolomics	isoleucylleucine/leucylisoleucine	52322
mlon_52340	mlon	metabolomics	N-carbamoylalanine	52340
mlon_52355	mlon	metabolomics	N-desmethyl tramadol	52355
mlon_52357	mlon	metabolomics	O-desmethyltramadol glucuronide	52357
mlon_52358	mlon	metabolomics	N,O-didesmethylvenlafaxine glucuronide	52358
mlon_52415	mlon	metabolomics	leucylphenylalanine/isoleucylphenylalanine	52415
mlon_52431	mlon	metabolomics	1-palmitoleoylglycerol (16:1)*	52431
mlon_52433	mlon	metabolomics	sphingomyelin (d17:1/16:0, d18:1/15:0, d16:1/17:0)*	52433
mlon_52434	mlon	metabolomics	palmitoyl dihydrosphingomyelin (d18:0/16:0)*	52434
mlon_52435	mlon	metabolomics	sphingomyelin (d18:2/23:0, d18:1/23:1, d17:1/24:1)*	52435
mlon_52436	mlon	metabolomics	tricosanoyl sphingomyelin (d18:1/23:0)*	52436
mlon_52437	mlon	metabolomics	sphingomyelin (d18:2/24:1, d18:1/24:2)*	52437
mlon_52438	mlon	metabolomics	1-stearoyl-2-oleoyl-GPC (18:0/18:1)	52438
mlon_52446	mlon	metabolomics	1-stearoyl-2-linoleoyl-GPE (18:0/18:2)*	52446
mlon_52447	mlon	metabolomics	1-stearoyl-2-arachidonoyl-GPE (18:0/20:4)	52447
mlon_52449	mlon	metabolomics	1-stearoyl-2-arachidonoyl-GPI (18:0/20:4)	52449
mlon_52450	mlon	metabolomics	1-palmitoyl-2-linoleoyl-GPI (16:0/18:2)	52450
mlon_52452	mlon	metabolomics	1-stearoyl-2-linoleoyl-GPC (18:0/18:2)*	52452
mlon_52454	mlon	metabolomics	1-palmitoyl-2-dihomo-linolenoyl-GPC	52454
			(16:0/20:3n3 or 6)*
mlon_52461	mlon	metabolomics	1-palmitoyl-2-oleoyl-GPC (16:0/18:1)	52461
mlon_52462	mlon	metabolomics	1-palmitoyl-2-arachidonoyl-GPC (16:0/20:4n6)	52462
mlon_52463	mlon	metabolomics	1-palmitoyl-2-eicosapentaenoyl-GPC (16:0/20:5)*	52463
mlon_52464	mlon	metabolomics	1-palmitoyl-2-arachidonoyl-GPE (16:0/20:4)*	52464
mlon_52465	mlon	metabolomics	1-palmitoyl-2-docosahexaenoyl-GPE (16:0/22:6)*	52465
mlon_52466	mlon	metabolomics	1-stearoyl-2-docosahexaenoyl-GPE (18:0/22:6)*	52466
mlon_52467	mlon	metabolomics	1-palmitoyl-2-arachidonoyl-GPI (16:0/20:4)*	52467
mlon_52468	mlon	metabolomics	1-stearoyl-2-linoleoyl-GPI (18:0/18:2)	52468
mlon_52470	mlon	metabolomics	1-palmitoyl-2-palmitoleoyl-GPC (16:0/16:1)*	52470
mlon_52471	mlon	metabolomics	1-palmitoyl-2-palmitoleoyl-GPE (16:0/16:1)*	52471
mlon_52473	mlon	metabolomics	gamma-tocopherol/beta-tocopherol	52473
mlon_52474	mlon	metabolomics	1-(1-enyl-palmitoyl)-GPC (P-16:0)*	52474
mlon_52475	mlon	metabolomics	1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (P-18:0/20:4)*	52475
mlon_52476	mlon	metabolomics	1-(1-enyl-stearoyl)-2-docosahexaenoyl-	52476
			GPE (P-18:0/22:6)*
mlon_52477	mlon	metabolomics	1-(1-enyl-palmitoyl)-2-oleoyl-GPE (P-16:0/18:1)*	52477
mlon_52478	mlon	metabolomics	1-(1-enyl-palmitoyl)-2-oleoyl-GPC (P-16:0/18:1)*	52478
mlon_52495	mlon	metabolomics	sphingomyelin (d18:1/21:0, d17:1/22:0, d16:1/23:0)*	52495
mlon_52497	mlon	metabolomics	1-pentadecanoyl-2-linoleoyl-GPC (15:0/18:2)*	52497
mlon_52499	mlon	metabolomics	1-margaroyl-2-oleoyl-GPC (17:0/18:1)*	52499
mlon_52500	mlon	metabolomics	1-margaroyl-2-linoleoyl-GPC (17:0/18:2)*	52500
mlon_52603	mlon	metabolomics	1,2-dilinoleoyl-GPC (18:2/18:2)	52603
mlon_52604	mlon	metabolomics	N-palmitoyl-sphinganine (d18:0/16:0)	52604
mlon_52605	mlon	metabolomics	sphinganine-1-phosphate	52605
mlon_52608	mlon	metabolomics	linoleoyl ethanolamide	52608
mlon_52610	mlon	metabolomics	1-palmitoyl-2-docosahexaenoyl-GPC (16:0/22:6)	52610
mlon_52611	mlon	metabolomics	1-stearoyl-2-docosahexaenoyl-GPC (18:0/22:6)	52611
mlon_52612	mlon	metabolomics	1-(1-enyl-stearoyl)-2-oleoyl-GPC (P-18:0/18:1)	52612
mlon_52613	mlon	metabolomics	1-(1-enyl-stearoyl)-2-arachidonoyl-GPC (P-18:0/20:4)	52613
mlon_52614	mlon	metabolomics	1-(1-enyl-stearoyl)-2-oleoyl-GPE (P-18:0/18:1)	52614
mlon_52615	mlon	metabolomics	sphingomyelin (d18:1/17:0, d17:1/18:0, d19:1/16:0)	52615
mlon_52616	mlon	metabolomics	1-palmitoyl-2-stearoyl-GPC (16:0/18:0)	52616
mlon_52623	mlon	metabolomics	1-stearoyl-2-oleoyl-GPG (18:0/18:1)	52623
mlon_52629	mlon	metabolomics	1-stearoyl-2-dihomo-linolenoyl-GPC	52629
			(18:0/20:3n3 or 6)*
mlon_52630	mlon	metabolomics	1-(1-enyl-palmitoyl)-2-docosahexaenoyl-	52630
			GPC (P-16:0/22:6)*
mlon_52631	mlon	metabolomics	palmitoleoyl-oleoyl-glycerol (16:1/18:1) [2]*	52631
mlon_52632	mlon	metabolomics	palmitoleoyl-oleoyl-glycerol (16:1/18:1) [1]*	52632
mlon_52633	mlon	metabolomics	palmitoyl-linoleoyl-glycerol (16:0/18:2) [1]*	52633
mlon_52634	mlon	metabolomics	palmitoyl-linoleoyl-glycerol (16:0/18:2) [2]*	52634
mlon_52668	mlon	metabolomics	1-stearoyl-2-docosahexaenoyl-GPI (18:0/22:6)*	52668
mlon_52669	mlon	metabolomics	1-palmitoyl-2-oleoyl-GPI (16:0/18:1)*	52669
mlon_52672	mlon	metabolomics	1-(1-enyl-palmitoyl)-2-docosahexaenoyl-	52672
			GPE (P-16:0/22:6)*
mlon_52673	mlon	metabolomics	1-(1-enyl-palmitoyl)-2-arachidonoyl-GPE	52673
			(P-16:0/20:4)*
mlon_52677	mlon	metabolomics	1-(1-enyl-palmitoyl)-2-linoleoyl-GPE (P-16:0/18:2)*	52677
mlon_52682	mlon	metabolomics	1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2)*	52682
mlon_52687	mlon	metabolomics	1-oleoyl-2-linoleoyl-GPE (18:1/18:2)*	52687
mlon_52689	mlon	metabolomics	1-(1-enyl-palmitoyl)-2-arachidonoyl-GPC	52689
			(P-16:0/20:4)*
mlon_52690	mlon	metabolomics	1-linoleoyl-GPA (18:2)*	52690
mlon_52697	mlon	metabolomics	1-oleoyl-2-docosahexaenoyl-GPC (18:1/22:6)*	52697
mlon_52698	mlon	metabolomics	1-adrenoyl-GPC (22:4)*	52698
mlon_52699	mlon	metabolomics	1-stearoyl-2-docosapentaenoyl-GPC (18:0/22:5n3)*	52699
mlon_527	mlon	metabolomics	lactate	527
mlon_52700	mlon	metabolomics	1-stearoyl-2-docosapentaenoyl-GPC (18:0/22:5n6)*	52700
mlon_52701	mlon	metabolomics	1-(1-enyl-oleoyl)-GPC (P-18:1)*	52701
mlon_52702	mlon	metabolomics	1-(1-enyl-stearoyl)-GPC (P-18:0)*	52702
mlon_52703	mlon	metabolomics	1-stearyl-GPC (O-18:0)*	52703
mlon_52704	mlon	metabolomics	1-(1-enyl-stearoyl)-2-docosahexaenoyl-	52704
			GPC (P-18:0/22:6)*
mlon_52705	mlon	metabolomics	1-oleoyl-2-dihomo-linolenoyl-GPC (18:1/20:3)*	52705
mlon_52706	mlon	metabolomics	1-palmitoyl-2-adrenoyl-GPC (16:0/22:4)*	52706
mlon_52707	mlon	metabolomics	1-myristoyl-2-linoleoyl-GPC (14:0/18:2)*	52707
mlon_52710	mlon	metabolomics	1-linoleoyl-2-arachidonoyl-GPC (18:2/20:4n6)*	52710
mlon_52712	mlon	metabolomics	1-(1-enyl-stearoyl)-2-linoleoyl-GPC (P-18:0/18:2)*	52712
mlon_52713	mlon	metabolomics	1-(1-enyl-palmitoyl)-2-palmitoleoyl-GPC	52713
			(P-16:0/16:1)*
mlon_52714	mlon	metabolomics	1-(1-enyl-palmitoyl)-2-dihomo-linolenoyl-	52714
			GPC (P-16:0/20:3)*
mlon_52715	mlon	metabolomics	1-(1-enyl-palmitoyl)-2-myristoyl-GPC (P-16:0/14:0)*	52715
mlon_52716	mlon	metabolomics	1-(1-enyl-palmitoyl)-2-palmitoyl-GPC (P-16:0/16:0)*	52716
mlon_52717	mlon	metabolomics	1-palmityl-2-oleoyl-GPC (0-16:0/18:1)*	52717
mlon_52718	mlon	metabolomics	1-palmityl-2-arachidonoyl-GPC (O-16:0/20:4)*	52718
mlon_52719	mlon	metabolomics	phosphatidylcholine (16:0/22:5n3, 18:1/20:4)*	52719
mlon_52726	mlon	metabolomics	1-stearoyl-2-oleoyl-GPI (18:0/18:1)*	52726
mlon_52748	mlon	metabolomics	1-(1-enyl-stearoyl)-2-linoleoyl-GPE (P-18:0/18:2)*	52748
mlon_528	mlon	metabolomics	alpha-ketoglutarate	528
mlon_52913	mlon	metabolomics	pregabalin	52913
mlon_52914	mlon	metabolomics	5-hydroxyindole sulfate	52914
mlon_52915	mlon	metabolomics	7-hydroxyindole sulfate	52915
mlon_52925	mlon	metabolomics	phenylacetylglutamate	52925
mlon_52929	mlon	metabolomics	3,4-methyleneheptanoylcarnitine	52929
mlon_52932	mlon	metabolomics	4-hydroxyphenylacetatoylcarnitine	52932
mlon_52944	mlon	metabolomics	palmitoylcholine	52944
mlon_52949	mlon	metabolomics	enalapril	52949
mlon_52954	mlon	metabolomics	sitagliptin	52954
mlon_52955	mlon	metabolomics	ezetimibe	52955
mlon_52958	mlon	metabolomics	rivaroxaban	52958
mlon_52974	mlon	metabolomics	glycochenodeoxycholate sulfate	52974
mlon_52975	mlon	metabolomics	glycodeoxycholate sulfate	52975
mlon_52983	mlon	metabolomics	glycochenodeoxycholate glucuronide (1)	52983
mlon_52984	mlon	metabolomics	3-hydroxybutyrylcarnitine (2)	52984
mlon_52988	mlon	metabolomics	adipoylcarnitine (C6-DC)	52988
mlon_52990	mlon	metabolomics	suberoylcarnitine (C8-DC)	52990
mlon_53	mlon	metabolomics	glutamine	53
mlon_53010	mlon	metabolomics	lactosyl-N-palmitoyl-sphingosine (d18:1/16:0)	53010
mlon_53013	mlon	metabolomics	glycosyl-N-palmitoyl-sphingosine (d18:1/16:0)	53013
mlon_53026	mlon	metabolomics	3,4-methyleneheptanoate	53026
mlon_53031	mlon	metabolomics	methylsuccinoylcarnitine	53031
mlon_531	mlon	metabolomics	3-hydroxy-3-methylglutarate	531
mlon_53174	mlon	metabolomics	1,2-dilinoleoyl-GPE (18:2/18:2)*	53174
mlon_53175	mlon	metabolomics	1-palmityl-2-linoleoyl-GPC (O-16:0/18:2)*	53175
mlon_53176	mlon	metabolomics	1-linoleoyl-2-linolenoyl-GPC (18:2/18:3)*	53176
mlon_53177	mlon	metabolomics	phosphatidylcholine (14:0/14:0, 16:0/12:0)	53177
mlon_53178	mlon	metabolomics	phosphatidylcholine (15:0/18:1, 17:0/16:1, 16:0/17:1)*	53178
mlon_53190	mlon	metabolomics	1-palmitoyl-2-eicosapentaenoyl-GPE (16:0/20:5)*	53190
mlon_53192	mlon	metabolomics	phosphatidylcholine (18:0/20:2, 20:0/18:2)*	53192
mlon_53193	mlon	metabolomics	1-margaroyl-2-arachidonoyl-GPC (17:0/20:4)*	53193
mlon_53194	mlon	metabolomics	1-pentadecanoyl-2-arachidonoyl-GPC (15:0/20:4)*	53194
mlon_53195	mlon	metabolomics	1-myristoyl-2-arachidonoyl-GPC (14:0/20:4)*	53195
mlon_53196	mlon	metabolomics	1-myristoyl-2-docosahexaenoyl-GPC (14:0/22:6)*	53196
mlon_53197	mlon	metabolomics	1-pentadecanoyl-2-docosahexaenoyl-GPC (15:0/22:6)*	53197
mlon_53198	mlon	metabolomics	1-margaroyl-2-docosahexaenoyl-GPC (17:0/22:6)*	53198
mlon_53199	mlon	metabolomics	1-linoleoyl-2-docosahexaenoyl-GPC (18:2/22:6)*	53199
mlon_53202	mlon	metabolomics	1-oleoyl-2-docosapentaenoyl-GPC (18:1/22:5n3)*	53202
mlon_53209	mlon	metabolomics	1-oleoyl-2-docosahexaenoyl-GPE (18:1/22:6)*	53209
mlon_53211	mlon	metabolomics	1-linoleoyl-2-docosapentaenyol-GPC (18:2/22:5n3)*	53211
mlon_53223	mlon	metabolomics	palmitoleoylcarnitine (C16:1)*	53223
mlon_53224	mlon	metabolomics	pimeloylcarnitine/3-methyladipoylcarnitine (C7-DC)	53224
mlon_53230	mlon	metabolomics	3-hydroxyhexanoate	53230
mlon_53231	mlon	metabolomics	thioproline	53231
mlon_53239	mlon	metabolomics	O-desmethyltramadol	53239
mlon_53241	mlon	metabolomics	tramadol	53241
mlon_53242	mlon	metabolomics	5-bromotryptophan	53242
mlon_53243	mlon	metabolomics	catechol glucuronide	53243
mlon_53254	mlon	metabolomics	caffeic acid sulfate	53254
mlon_53257	mlon	metabolomics	palmitoloelycholine	53257
mlon_53260	mlon	metabolomics	oleoylcholine	53260
mlon_53261	mlon	metabolomics	arachidonoylcholine	53261
mlon_53262	mlon	metabolomics	dihomo-linolenoyl-choline	53262
mlon_53263	mlon	metabolomics	docosahexaenoylcholine	53263
mlon_54	mlon	metabolomics	tryptophan	54
mlon_542	mlon	metabolomics	3-hydroxybutyrate (BHBA)	542
mlon_54742	mlon	metabolomics	prednisolone	54742
mlon_54745	mlon	metabolomics	cetirizine	54745
mlon_54762	mlon	metabolomics	lamotrigine	54762
mlon_54784	mlon	metabolomics	chlorthalidone	54784
mlon_54805	mlon	metabolomics	3beta-hydroxy-5-cholestenoate	54805
mlon_54812	mlon	metabolomics	1-palmitoyl-2-gamma-linolenoyl-GPC (16:0/18:3n6)*	54812
mlon_54885	mlon	metabolomics	1-linoleoyl-GPG (18:2)*	54885
mlon_54907	mlon	metabolomics	hexanoylglutamine	54907
mlon_54910	mlon	metabolomics	vanillactate	54910
mlon_54923	mlon	metabolomics	beta-citrylglutamate	54923
mlon_54942	mlon	metabolomics	palmitoyl-oleoyl-glycerol (16:0/18:1) [2]*	54942
mlon_54943	mlon	metabolomics	palmitoyl-oleoyl-glycerol (16:0/18:1) [1]*	54943
mlon_54945	mlon	metabolomics	oleoyl-oleoyl-glycerol (18:1/18:1) [1]*	54945
mlon_54946	mlon	metabolomics	oleoyl-oleoyl-glycerol (18:1/18:1) [2]*	54946
mlon_54953	mlon	metabolomics	diacylglycerol (14:0/18:1, 16:0/16:1) [1]*	54953
mlon_54954	mlon	metabolomics	diacylglycerol (14:0/18:1, 16:0/16:1) [2]*	54954
mlon_54955	mlon	metabolomics	linoleoyl-arachidonoyl-glycerol (18:2/20:4) [1]*	54955
mlon_54956	mlon	metabolomics	linoleoyl-arachidonoyl-glycerol (18:2/20:4) [2]*	54956
mlon_54957	mlon	metabolomics	palmitoyl-arachidonoyl-glycerol (16:0/20:4) [1]*	54957
mlon_54958	mlon	metabolomics	palmitoyl-arachidonoyl-glycerol (16:0/20:4) [2]*	54958
mlon_54960	mlon	metabolomics	oleoyl-arachidonoyl-glycerol (18:1/20:4) [1]*	54960
mlon_54961	mlon	metabolomics	oleoyl-arachidonoyl-glycerol (18:1/20:4) [2]*	54961
mlon_54963	mlon	metabolomics	linoleoyl-linolenoyl-glycerol (18:2/18:3) [1]*	54963
mlon_54964	mlon	metabolomics	linoleoyl-linolenoyl-glycerol (18:2/18:3) [2]*	54964
mlon_54966	mlon	metabolomics	diacylglycerol (16:1/18:2 [2], 16:0/18:3 [1])*	54966
mlon_54967	mlon	metabolomics	palmitoleoyl-linoleoyl-glycerol (16:1/18:2) [1]*	54967
mlon_54968	mlon	metabolomics	linoleoyl-linoleoyl-glycerol (18:2/18:2) [1]*	54968
mlon_54969	mlon	metabolomics	linoleoyl-linoleoyl-glycerol (18:2/18:2) [2]*	54969
mlon_54970	mlon	metabolomics	oleoyl-linolenoyl-glycerol (18:1/18:3) [2]*	54970
mlon_54979	mlon	metabolomics	N-stearoyl-sphingosine (d18:1/18:0)*	54979
mlon_54984	mlon	metabolomics	1-stearoyl-2-dihomo-linolenoyl-GPI	54984
			(18:0/20:3n3 or 6)*
mlon_54990	mlon	metabolomics	palmitoyl-palmitoyl-glycerol (16:0/16:0) [2]*	54990
mlon_55	mlon	metabolomics	beta-alanine	55
mlon_55003	mlon	metabolomics	1-myristoyl-2-palmitoleoyl-GPC (14:0/16:1)*	55003
mlon_55007	mlon	metabolomics	1-palmityl-GPE (O-16:0)*	55007
mlon_55015	mlon	metabolomics	gamma-glutamyl-alpha-lysine	55015
mlon_55017	mlon	metabolomics	4-hydroxyphenylacetylglutamine	55017
mlon_55037	mlon	metabolomics	1-(1-enyl-oleoyl)-2-docosahexaenoyl-GPE	55037
			(P-18:1/22:6)*
mlon_55040	mlon	metabolomics	1-palmityl-2-stearoyl-GPC (O-16:0/18:0)*	55040
mlon_55061	mlon	metabolomics	1-stearoyl-2-adrenoyl-GPC (18:0/22:4)*	55061
mlon_55062	mlon	metabolomics	1-arachidoyl-2-arachidonoyl-GPC (20:0/20:4)*	55062
mlon_55070	mlon	metabolomics	1-erucoyl-GPC (22:1)*	55070
mlon_55072	mlon	metabolomics	2-oxoarginine*	55072
mlon_553	mlon	metabolomics	cotinine	553
mlon_554	mlon	metabolomics	adenine	554
mlon_555	mlon	metabolomics	adenosine	555
mlon_558	mlon	metabolomics	adenosine 5′-diphosphoribose (ADP-ribose)	558
mlon_56	mlon	metabolomics	cystine	56
mlon_566	mlon	metabolomics	phenylpyruvate	566
mlon_568	mlon	metabolomics	biotin	568
mlon_569	mlon	metabolomics	caffeine	569
mlon_57	mlon	metabolomics	glutamate	57
mlon_57317	mlon	metabolomics	1-palmitoleoyl-2-arachidonoyl-GPC (16:1/20:4)*	57317
mlon_57330	mlon	metabolomics	lignoceroyl sphingomyelin (d18:1/24:0)	57330
mlon_57331	mlon	metabolomics	behenoyl dihydrosphingomyelin (d18:0/22:0)*	57331
mlon_57332	mlon	metabolomics	1-palmityl-2-palmitoyl-GPC (O-16:0/16:0)*	57332
mlon_57333	mlon	metabolomics	1-stearyl-2-arachidonoyl-GPC (O-18:0/20:4)*	57333
mlon_57334	mlon	metabolomics	1-stearyl-2-docosapentaenoyl-GPC (O-18:0/22:5n3)*	57334
mlon_57335	mlon	metabolomics	phosphatidylcholine (16:0/20:4n3; 18:1/18:3n6)*	57335
mlon_57336	mlon	metabolomics	1-stearoyl-2-dihomo-linolenoyl-GPE	57336
			(18:0/20:3n3 or 6)*
mlon_57338	mlon	metabolomics	1-stearoyl-2-docosapentaenoyl-GPE (18:0/22:5n6)*	57338
mlon_57339	mlon	metabolomics	1-stearoyl-2-adrenoyl-GPE (18:0/22:4)*	57339
mlon_57342	mlon	metabolomics	1-(1-enyl-stearoyl)-2-docosapentaenoyl-	57342
			GPE (P-18:0/22:5n3)*
mlon_57343	mlon	metabolomics	1-(1-enyl-stearoyl)-2-dihomo-linolenoyl-	57343
			GPE (P-18:0/20:3)*
mlon_57365	mlon	metabolomics	myristoyl dihydrosphingomyelin (d18:0/14:0)*	57365
mlon_57370	mlon	metabolomics	lactosyl-N-nervonoyl-sphingosine (d18:1/24:1)*	57370
mlon_57372	mlon	metabolomics	N-behenoyl-sphingadienine (d18:2/22:0)*	57372
mlon_57373	mlon	metabolomics	palmitoyl-docosahexaenoyl-glycerol (16:0/22:6) [1]*	57373
mlon_57406	mlon	metabolomics	palmitoleoyl-arachidonoyl-glycerol (16:1/20:4) [2]*	57406
mlon_57407	mlon	metabolomics	myristoyl-linoleoyl-glycerol (14:0/18:2) [1]*	57407
mlon_57408	mlon	metabolomics	myristoyl-linoleoyl-glycerol (14:0/18:2) [2]*	57408
mlon_57411	mlon	metabolomics	phosphatidylethanolamine (P-18:1/20:4, P-	57411
			16:0/22:5n3)*
mlon_57415	mlon	metabolomics	1-palmitoyl-2-(hydroxylinoleoyl)-GPC	57415
			(16:0/18:2(OH))*
mlon_57421	mlon	metabolomics	glycosyl-N-behenoyl-sphingadienine (d18:2/22:0)*	57421
mlon_57426	mlon	metabolomics	sphingadienine	57426
mlon_57428	mlon	metabolomics	hexadecasphingosine (d16:1)*	57428
mlon_57430	mlon	metabolomics	N-palmitoyl-heptadecasphingosine (d17:1/16:0)*	57430
mlon_57432	mlon	metabolomics	ceramide (d18:1/14:0, d16:1/16:0)*	57432
mlon_57434	mlon	metabolomics	ceramide (d18:1/17:0, d17:1/18:0)*	57434
mlon_57437	mlon	metabolomics	ceramide (d16:1/24:1, d18:1/22:1)*	57437
mlon_57440	mlon	metabolomics	ceramide (d18:1/20:0, d16:1/22:0, d20:1/18:0)*	57440
mlon_57443	mlon	metabolomics	ceramide (d18:2/24:1, d18:1/24:2)*	57443
mlon_57448	mlon	metabolomics	glycosyl ceramide (d18:1/23:1, d17:1/24:1)*	57448
mlon_57449	mlon	metabolomics	stearoyl-arachidonoyl-glycerol (18:0/20:4) [2]*	57449
mlon_57450	mlon	metabolomics	stearoyl-arachidonoyl-glycerol (18:0/20:4) [1]*	57450
mlon_57453	mlon	metabolomics	glycosyl ceramide (d18:2/24:1, d18:1/24:2)*	57453
mlon_57457	mlon	metabolomics	glycosyl ceramide (d16:1/24:1, d18:1/22:1)*	57457
mlon_57461	mlon	metabolomics	argininate*	57461
mlon_57463	mlon	metabolomics	linoleoylcholine*	57463
mlon_57464	mlon	metabolomics	stearoylcholine*	57464
mlon_57473	mlon	metabolomics	sphingomyelin (d18:0/18:0, d19:0/17:0)*	57473
mlon_57474	mlon	metabolomics	sphingomyelin (d18:2/18:1)*	57474
mlon_57475	mlon	metabolomics	sphingomyelin (d18:1/19:0, d19:1/18:0)*	57475
mlon_57476	mlon	metabolomics	sphingomyelin (d18:0/20:0, d16:0/22:0)*	57476
mlon_57477	mlon	metabolomics	sphingomyelin (d18:1/22:2, d18:2/22:1, d16:1/24:2)*	57477
mlon_57478	mlon	metabolomics	sphingomyelin (d18:1/25:0, d19:0/24:1,	57478
			d20:1/23:0, d19:1/24:0)*
mlon_57479	mlon	metabolomics	sphingomyelin (d18:2/24:2)*	57479
mlon_57480	mlon	metabolomics	sphingomyelin (d18:2/21:0, d16:2/23:0)*	57480
mlon_57481	mlon	metabolomics	sphingomyelin (d18:1/20:2, d18:2/20:1, d16:1/22:2)*	57481
mlon_57482	mlon	metabolomics	sphingomyelin (d18:2/23:1)*	57482
mlon_57483	mlon	metabolomics	sphingomyelin (d17:2/16:0, d18:2/15:0)*	57483
mlon_575	mlon	metabolomics	arabinose	575
mlon_57509	mlon	metabolomics	1-linolenoyl-GPE (18:3)*	57509
mlon_57511	mlon	metabolomics	linolenoylcarnitine (C18:3)*	57511
mlon_57512	mlon	metabolomics	margaroylcarnitine (C17)*	57512
mlon_57513	mlon	metabolomics	arachidoylcarnitine (C20)*	57513
mlon_57514	mlon	metabolomics	behenoylcarnitine (C22)*	57514
mlon_57515	mlon	metabolomics	lignoceroylcarnitine (C24)*	57515
mlon_57516	mlon	metabolomics	cerotoylcarnitine (C26)*	57516
mlon_57517	mlon	metabolomics	ximenoylcarnitine (C26:1)*	57517
mlon_57518	mlon	metabolomics	arachidonoylcarnitine (C20:4)	57518
mlon_57519	mlon	metabolomics	eicosenoylcarnitine (C20:1)*	57519
mlon_57520	mlon	metabolomics	dihomo-linoleoylcarnitine (C20:2)*	57520
mlon_57521	mlon	metabolomics	dihomo-linolenoylcarnitine (C20:3n3 or 6)*	57521
mlon_57523	mlon	metabolomics	docosahexaenoylcarnitine (C22:6)*	57523
mlon_57528	mlon	metabolomics	adrenoylcarnitine (C22:4)*	57528
mlon_57531	mlon	metabolomics	nervonoylcarnitine (C24:1)*	57531
mlon_57547	mlon	metabolomics	2,3-dihydroxy-2-methylbutyrate	57547
mlon_57564	mlon	metabolomics	perfluorooctanesulfonate (PFOS)	57564
mlon_57577	mlon	metabolomics	isoursodeoxycholate	57577
mlon_57591	mlon	metabolomics	beta-cryptoxanthin	57591
mlon_57595	mlon	metabolomics	glycosyl ceramide (d18:1/20:0, d16:1/22:0)*	57595
mlon_57603	mlon	metabolomics	1-nervonoyl-2-arachidonoyl-GPC (24:1/20:4)*	57603
mlon_57614	mlon	metabolomics	ciprofloxacin	57614
mlon_57635	mlon	metabolomics	carotene diol (1)	57635
mlon_57636	mlon	metabolomics	carotene diol (2)	57636
mlon_57637	mlon	metabolomics	carotene diol (3)	57637
mlon_57641	mlon	metabolomics	levetiracetam	57641
mlon_57652	mlon	metabolomics	hexadecadienoate (16:2n6)	57652
mlon_57655	mlon	metabolomics	2′-O-methyluridine	57655
mlon_57659	mlon	metabolomics	N-palmitoylserine	57659
mlon_57664	mlon	metabolomics	N-oleoylserine	57664
mlon_57687	mlon	metabolomics	N,N,N-trimethyl-5-aminovalerate	57687
mlon_57691	mlon	metabolomics	trazadone	57691
mlon_57707	mlon	metabolomics	fluconazole	57707
mlon_57709	mlon	metabolomics	ADSGEGDFXAEGGGVR*	57709
mlon_57778	mlon	metabolomics	2-propyl-2-pentenoate (2-ene-valproate)	57778
mlon_57781	mlon	metabolomics	3-hydroxyvalproate	57781
mlon_58	mlon	metabolomics	glycine	58
mlon_587	mlon	metabolomics	gluconate	587
mlon_59	mlon	metabolomics	histidine	59
mlon_590	mlon	metabolomics	hypotaurine	590
mlon_594	mlon	metabolomics	nicotinamide	594
mlon_5983	mlon	metabolomics	corticosterone	5983
mlon_60	mlon	metabolomics	leucine	60
mlon_601	mlon	metabolomics	dihydroorotate	601
mlon_605	mlon	metabolomics	uracil	605
mlon_606	mlon	metabolomics	uridine	606
mlon_607	mlon	metabolomics	trans-urocanate	607
mlon_6146	mlon	metabolomics	2-aminoadipate	6146
mlon_61832	mlon	metabolomics	5-hydroxyvalproate	61832
mlon_61844	mlon	metabolomics	morphine-3-glucuronide	61844
mlon_61845	mlon	metabolomics	morphine-6-glucuronide	61845
mlon_62479	mlon	metabolomics	citalopram propionate*	62479
mlon_62480	mlon	metabolomics	4-hydroxy duloxetine glucuronide*	62480
mlon_62481	mlon	metabolomics	5-hydroxy-6-methoxy duloxetine sulfate*	62481
mlon_62483	mlon	metabolomics	ezetimibe glucuronide *	62483
mlon_62484	mlon	metabolomics	N-desalkylquetiapine*	62484
mlon_62485	mlon	metabolomics	ranitidine N-oxide*	62485
mlon_63	mlon	metabolomics	cholesterol	63
mlon_64	mlon	metabolomics	phenylalanine	64

Protein or Polypeptide Data

Disclosed herein are algorithms, classifiers, or models that generate classifications of individuals based on input data including protein or polypeptide data. Protein or polypeptide data can include information regarding the identity and/or quantity of one or more proteins or polypeptides obtained from a biological sample. In some embodiments, the data is obtained using proteomics techniques such as ELISA, proximity extension assay (PEA), mass spectrometry. In some embodiments, the data is obtained using antibodies that recognize the one or more proteins or polypeptides. Various techniques allow for multiplex analysis of a plurality of proteins or polypeptides in a single sample such as, for example, multiple reaction monitoring (MRM) mass spectrometry, ELISA, proximity extension assay, Western Blot, and protein detection techniques used in the field. In some embodiments, the protein or polypeptide data comprises information for a protein panel. The protein panel can be configured to address specific inquiries such as, for example, having protein biomarkers linked to cardiovascular health for purposes of assessing a heart condition.

In some embodiments, the protein panel comprises a list of proteins such as the ones provided by Olink Proteomics. In some embodiments, the protein panel comprises a cardiometabolic panel. In some embodiments, the protein panel comprises a cell regulation panel. In some embodiments, the protein panel comprises a cardiovascular panel. In some embodiments, the protein panel comprises a development panel. In some embodiments, the protein panel comprises an immune response panel. In some embodiments, the protein panel comprises an immune-oncology panel. In some embodiments, the protein panel comprises an inflammation panel. In some embodiments, the protein panel comprises a metabolism panel. In some embodiments, the protein panel comprises a neurology panel. In some embodiments, the protein panel comprises an oncology panel. In some embodiments, the protein panel comprises an organ damage panel.

In some embodiments, the protein panel comprises a plurality of proteins or polypeptide biomarkers. In some embodiments, the protein panel comprises at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more proteins or polypeptides. In some embodiments, the protein panel comprises a shortened or filtered group of proteins or polypeptides. In some embodiments, the protein panel comprises a reduced group of proteins or polypeptides generated by curating an initial group of proteins or polypeptides for targeted properties or associations. For example, an initial group of proteins linked to ALS may be curated to generate a filtered list of proteins that has more robust experimental support for a causative role in ALS. Accordingly, in some embodiments, the protein panel (e.g., a reduced or filtered panel) has no more than 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, or no more than 200 proteins or polypeptides.

Gene Expression Data

Disclosed herein are algorithms, classifiers, or models that generate classifications of individuals based on input data including RNA sequencing and/or expression data. In some embodiments, input data is generated by performing RNA sequencing on a biological sample obtained from a subject. The input data can be generated using any number of available laboratory techniques including reverse transcriptase quantitative PCR (RT-qPCR) and various RNA sequencing technologies. Examples of RNA sequencing include mRNA sequencing, small RNA sequencing, whole RNA sequencing, targeted RNA sequencing, RNA exome targeted sequencing, and single-cell RNA sequencing. Small RNA sequencing targets small RNA molecules such as microRNA. Whole RNA sequencing targets the RNA transcripts in the transcriptome, and includes both coding and noncoding RNA. Targeted RNA sequencing allows for the selecting and sequencing of specific transcripts of interest using targeted enrichment or targeted amplicon. RNA exome capture sequencing enriches for the coding regions of the transcriptome. In some embodiments, the RNA data comprises information for a genetic panel. The genetic panel can be configured to address specific inquiries such as, for example, having genetic biomarkers linked to cardiovascular health for purposes of assessing a heart condition.

In some embodiments, the genetic panel comprises a list of genes or transcripts having some link or association with one or more health conditions or traits. In some embodiments, the genetic panel comprises RNA sequencing information for a plurality of genes or transcripts. In some embodiments, the genetic panel comprises a cardiometabolic panel. In some embodiments, the genetic panel comprises a cell regulation panel. In some embodiments, the genetic panel comprises a cardiovascular panel. In some embodiments, the genetic panel comprises a development panel. In some embodiments, the genetic panel comprises an immune response panel. In some embodiments, the genetic panel comprises an immune-oncology panel. In some embodiments, the genetic panel comprises an inflammation panel. In some embodiments, the genetic panel comprises a metabolism panel. In some embodiments, the genetic panel comprises a neurology panel. In some embodiments, the genetic panel comprises an oncology panel. In some embodiments, the genetic panel comprises an organ damage panel.

In some embodiments, the genetic panel comprises a plurality of genetic biomarkers. In some embodiments, the genetic panel comprises at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, or more genes or transcripts. In some embodiments, the genetic panel comprises a shortened or filtered group of genes or transcripts. In some embodiments, the genetic panel comprises a reduced group of genes generated by curating an initial group of genes or transcripts for targeted properties or associations. For example, an initial group of genes or transcripts linked to ALS may be curated to generate a filtered list of genes or transcripts that has more robust experimental support for a causative role in ALS. Accordingly, in some embodiments, the genetic panel (e.g., a reduced or filtered panel) has no more than 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, or no more than 200 genes or transcripts.

Feature Selection

Disclosed herein are algorithms, classifiers, or models that generate classifications of individuals based on input data. The algorithms, classifiers, or models incorporate various features such as, for example, one or more biomarkers selected from protein levels, RNA transcript levels, and/or metabolite levels obtained from a biological sample of a subject. The features can be selected through analyzing data obtained for an initial feature set to identify the features that are significantly associated with the biological trait of interest. Using prior knowledge and/or data-driven methods, such features can be selected prior to the application of machine learning algorithms to generate trained models. In some embodiments, features are using certain data transformations such as, for example, principal component analysis.

In some embodiments, an initial feature set is generated by selecting or screening for all biomarkers known to have some association with a particular biological trait or combination of traits. In some embodiments, the initial feature set is generated by mining scientific publications or studies. For example, loose statistical associations from large-scale screening may generate statistical noise that makes it difficult to identify relevant biomarkers as features for the model. Thus, in some cases, prior knowledge from scientific publications is used to screen for relevant features. As an example, diabetes type 2, ALS, and MS models can be constructed based on publications that identified key biomarkers as indicators of these particular diseases or disorders. In some embodiments, feature selection comprises screening for or identifying features from scientific publications. In some embodiments, feature selection comprises screening for or identifying features from one or more databases. In some embodiments, the one or more databases comprises annotation(s) of one or more biomarkers. In some embodiments, feature selection comprises screening for or identifying features based on annotation(s) from one or more databases.

The annotation(s) can be a gene ontology of a particular biomarker such as an RNA transcript or a gene. The annotation or gene ontology for a biomarker can provide information about its function or relationship with other markers. As an example, the Gene Ontology (GO) resource provides a comprehensive knowledge base on genes and their products. In some embodiments, the gene ontology is represented as a keyword(s) or an identifier (a number, letter, or other unique combination of characters). The gene ontology can refer to a cellular component such as the parts of the cell or its extracellular environment associated with the biomarker. Illustrative and non-limiting examples of cellular components include cell junction, chromatin, membrane, organelle, or other component of the cell. In some embodiments, the gene ontology refers to a molecular function, which refers to the activities of the biomarker at the molecular level such as, for example, a chemical reaction catalyzed by the enzyme protein product of a gene or a binding activity of a transcription factor. Illustrative and non-limiting examples of molecular functions include antioxidant activity, protein folding chaperone, transcription regulator activity, and various other functions. In some embodiments, the gene ontology refers to a biological process, which refers to a set or sequence of one or more molecular activities that together play some role in the functioning of a living organism or component thereof. Illustrative and non-limiting examples of biological processes include actin filament polymerization, detoxification, hematopoiesis, phosphorus utilization, signaling, and various other processes. The annotation or gene ontology can be tiered or structured to provide more general information and/or more detailed information. For example, some biomarkers may be annotated with a cellular component gene ontology tag for cell junction, but a subset of these biomarkers may be further tagged with adherens junction while other biomarkers are instead tagged with desmosome depending on the specific cellular structure these individual biomarkers are associated with.

In some embodiments, the annotation for a biomarker is obtained from a database comprising biological pathway information. The database can include pathway maps of the relationships between genes or gene products and other biological molecules such as, for example, metabolites. As an example, the KEGG pathway database provides biological pathways that model molecular interactions between biological components. The pathway maps can include various types of information for biomarkers including genes, proteins, RNAs, chemical compounds, glycans, and chemical reactions. In some embodiments, additional information such as mutations associated with diseases and drug targets are included. In some embodiments, the pathway maps are classified into the sub-sections such as metabolism, genetic information processing (e.g., transcription, translation, replication, etc.), environmental information processing (e.g., signal transduction), cellular processes (e.g., cell proliferation), organismal systems (e.g., immune system), human diseases, and drug development.

In some embodiments, the systems, methods, and software disclosed herein utilize an automated or semi-automated feature selection process by which features are selected based on third party annotations such as gene ontology tags. In some embodiments, the features are at least partially selected or screened based on one or more annotations. In some embodiments, the biomarker(s) are annotated or associated with a gene ontology based on one or more tags or labels. These tags or labels can be standardized and formatted to facilitate automated or semi-automated analysis such as, for example, extraction and/or processing. In some embodiments, one or more biomarkers are extracted from a third party database based on one or more annotations. In some embodiments, the biomarkers are further processed or selected based on scientific publications to arrive at an initial feature set. This feature set can be trained using labeled data by a machine learning algorithm to generate a model and/or select for the most significantly associated features for a disease, disorder, or condition, or other trait. In some embodiments, feature selection comprises screening for biomarkers based on KEGG and/or GO annotations.

In some embodiments, the systems, methods, and software disclosed herein comprise a feature selection or feature transformation process. A goal of feature selection is to reduce the size of the feature set while retaining as much useful information as possible. In some embodiments, feature selection comprises filtering out or removing features based on variance. Such techniques include principal component analysis (PCA), partial least squares (PLS) regression, and independent component analysis (ICA).

Non-Molecular Data

Although various algorithms described herein utilize molecular information such as metabolite data to generate classifications of individuals, non-assayed information can also be used. The combination of molecular data and non-molecular data can be useful in enhancing classifier performance. For example, age and sex can serve as important discriminatory features for accurately classifying an individual. Non-molecular data can include patient information such as demographic information. In some cases, classifiers or machine learning models utilize data comprising non-molecular data such as, for example, age or age range, race, ethnicity, nationality, sex, smoking status, weight, body mass index (BMI), exercise (e.g., frequency, duration, and/or intensity), hobbies, household income, geographic location, disabilities, education, employment status, health status (e.g. a confirmed cancer diagnosis), children, marital status, or any combination thereof.

Non-molecular data can include measurable health parameters. Examples of health parameters include heart rate, blood pressure, body temperature, body fat percentage, height, waistline, VO2 max, and other relevant parameters.

Traits

Disclosed herein are algorithms, classifiers, or models that generate classifications or predictions pertaining to one or more traits. Traits are non-molecular information about a subject that can be related to the subject's general well-being or health status. In some embodiments, traits are not directed to a particular disease or disease spectrum. Examples of traits include non-molecular data such as age, sex, body mass index (BMI), race, ethnicity, personality traits, family history, and other measurable health parameters or demographics. Traits can be selected from or organized into various categories including personal characteristics, general health, mental health, health behaviors, interventions (e.g., treatments and therapies), systems (e.g., organ systems), environmental (e.g., work environment), conditions (e.g., diagnostic history), and other categories related to general health and well-being. In some embodiments, the algorithms, classifiers, or models disclosed herein are trained on data pertaining to one or more traits.

Accordingly, in some embodiments, predictions are generated for individuals that provide an assessment (e.g., a regression score) of one or more traits. In some embodiments, the prediction is an assessment of a composite well-being for an individual that incorporates multiple traits. In some embodiments, the prediction incorporates information about one or more traits to provide an assessment of one or more other traits. As an example, trait information or data for sleep, diet, and sun exposure may be included in a data set along with the “thrive” trait (e.g., a general assessment of health and well-being) that is used to train a model to predict a “thrive” assessment or score based at least in part on the trait information. In some embodiments, the model is trained to assess one or more traits using molecular data and/or trait information. As an example, a model can be trained to incorporate protein levels and RNA sequencing data in providing an assessment of an individual for a particular trait such as anxiety.

Alternatively, in some embodiments, predictions or classifications of a disease, disorder, or condition is generated based on input data incorporating trait information. In some embodiments, the systems, methods, and software disclosed herein identify certain traits that are significantly associated with or predictive of some mental health conditions such as depression. As an illustrative example, trait information for fitness and sleep may be identified as being associated with depression. Trait information and other data types such as molecular data can be combined as features in a single model or multiple models. In some embodiments, the model(s) undergoes machine learning using training data that incorporates trait information and/or molecular data such as RNA sequencing data and/or protein quantification. As a result, predictions can be generated that provide an assessment or evaluation of one or more traits and/or one or more diseases, disorders, or conditions. As an example, certain trait information may be associated with a particular disease or disorder that the subject is unaware of such as ALS.

In some embodiments, the systems, methods, and software disclosed herein incorporate input data including molecular data to generate predictions or evaluations of one or more traits. As an illustrative example, a model or algorithm undergoes machine learning using training data that includes metabolite data for individuals along with trait information relating to smoking, past smoking, alcohol load, amount of sleep, hours awake, or acute infection(s). Accordingly, certain metabolite levels can be identified as relevant to certain traits which can, for example, provide a metabolite signature for smokers. In some embodiments, the trait-related predictions or evaluations provided by the algorithms, models, or classifiers disclosed herein comprise a regression (e.g., a numerical or continuous output) instead of a classification (e.g., a categorical output such as yes/no).

In some embodiments, the systems, methods, and software disclosed herein incorporate input data such as patient-generated health data alone or in combination with other types of data (e.g., molecular data). In some embodiments, training data pertaining to one or more traits include a subject's self-assessment of a trait such as responses to questions. Trait information can include patient-generated health data. In some cases, trait information comprises yes/no responses to questions. In some cases, trait information comprises a response that is a number or score (e.g., an acute pain self-assessment from 1 to 10 with 10 being the highest possible level of pain). Examples of trait categories, traits, questions, and responses are provided in Table 3.

TABLE 3
Traits
Category	Trait		Question	Score
Personal	Sex			F/M
characteristics	Age			Chronological age
	BMI		weight at day of draw; height	weight (in
				kilograms) over your
				height squared (in
				centimeters)
	Race
	Ethnicity
	Personality
	traits
General	Family history
Health	Current	Reported
	conditions	conditions
	(not including
	acute
	conditions)
	Acute		Do you have any infections	by the conditions
	infection		right now (that you know of)?
			(B)
			What kind of respiratory
			infection do you have (or think
			you have)? (B)
			What kind of gastrointestinal
			infection do you have (or think
			you have)? (B)
	Allergies
	Perceived	Overall	Over the last month, how has	5 levels
	health	perceived	your health has been (B)
		health
		Impact of	Over the last month, how much
		condition	has your <condition> affected
			your life? (B)
		Health	Over the last month, how has
		change	your health changed? (B)
	Circadian		How long ago did you wake up
	cycle		for the day (and not go back to
			sleep again?) (B)
			How much sleep did you get
			last night? (B)
	Menstrual		Which of the following best	Exclude I do have
	cycle		describes your menstruation?	menstrual periods
			When did your last menstrual	because of birth
			period start? (B)	control OR I am past
				menopause, or I
				have had artificially-
				induced menopause
				OR This question
				doesn't apply to me
	Genetic
	predisposition
	Thrive	Thrive	Over the last month, how well
		ability	could you think, concentrate,
			and remember things? (B)
			Over the last month, how well
			could you control your
			emotions?
			Over the last month, how well
			could you take care of your
			personal needs?
			Over the last month, how well
			could you meet your
			responsibilities at work, school
			or home?
			Over the last month, how well
			could you participate in your
			favorite social and leisure
			activities?
		Thrive core	Please rate the severity of any
		symptoms	pain over the past month
			Please rate the severity of any
			depressed mood over the past
			month
			Please rate the severity of any
			anxious mood over the past
			month
			Please rate the severity of any
			fatigue over the past month
			Please rate the severity of any
			stress over the past month
		Thrive	Over the last month, how well
		mobility	could you walk without
			support?
			Over the last month, how well
			could you climb stairs?
		Thriving	Over the last month, how often
		experience	did you feel good about
			yourself?
			Over the last month, how often
			did you find meaning in your
			life?
			Over the last month, how often
			did you feel connected to
			others?
			Over the last month, how often
			did you feel able to live the life
			your wanted
Mental	Cognition		over the last month, how well	5 levels
Health			could you think, concentrate,
			and remember things? (B)
	Energy
	Depression		Please rare the severity of any
			depressive mood over the past
			month
	Anxiety		Please rate the severity of any
			anxious mood over the past
			month
	Stress		Please rate the severity of any
			stress over the past month
	Coping ability	stress,	Please rate the severity of any
	(mental	anxiety,	stress over the past month
	resilience)	depression,	Please rate the severity of any
		control	anxious mood over the past
		emotions	month
			Please rate the severity of any
			anxious mood over the past
			month
			Over the last month, how well
			could you control your
			emotions?
	Feel good/bad	pain and	Please rate the severity of any
		fatigue	fatigue over the past month
			Please rate the severity of any
			pain over the past month
Health	Fitness		Over the last month, how well	Not at all = 0
behaviors			could you lift heavy things? (A)	Poorly = 1
			Over the last month, for how	fairly well = 2
			long could you do exercise that	very well = 3
			made you breathe hard? (A)	extremely well = 4
	Substances	Smoke now	Some common substances can	yes to Tobacco
		(are you on	affect what appears in your	less than 24 h
		nicotine	blood. Which of these have you	less than 24 h
		now)	used in the last 24 hours? (B)
			How long ago did you last take
			nicotine other than tobacco? (B)
			How long ago did you last take
			tobacco? (B)
		Past smoking	Do you smoke? (A)	No, but I used to OR
			Did you ever smoke cigarettes	No I never smoked
			regularly (at least one cigarette	AND
			per day)? (A)	Yes
			Did you ever smoke at least one	OR
			pack of cigarettes a day? (A)	yes
		Past heavy	Do you smoke? (A)	No, but I used to OR
		Smoking	Did you ever smoke cigarettes	No I never smoked
		now	regularly (at least one cigarette	AND
			per day)? (A)	group smoke
			Did you ever smoke at least one	regularly AND at
			pack of cigarettes a day? (A)	least one pack Vs no
				smoked regularly
				AND no to one pack
				a day
		Alcohol	Some common substances can	no to alcohol
		Load	affect what appears in your	Exclude less than
			blood. Which of these have you	24 h
			used in the last 24 hours? (B)
			How long ago did you have
			alcohol? (B)
			How many drinks did you
			have? (B)
		Recreational	Some common substances can	yes to Drugs not
		drug now	affect what appears in your	listed in my profile
			blood. Which of these have you	as treatment
			used in the last 24 hours? (B)
		Recreational	Some common substances can	Exclude Drugs in the
		drug past	affect what appears in your	last 24 h
			blood. Which of these have you	yes to use any of
			used in the last 24 hours? (B)	these to manage
			Do you use any of these	disease
			“recreational” drugs to manage
			your disease? Please select all
			that apply (B)
		Caffeine	How long ago did you have	hours
		load (time	caffeine? (B)
		since
		caffeine)
	Sleep	Sleep load	How much sleep did you get	hours
		last night	last night? (B)
		Sleep quality	Over the last month, how well
			could you fall asleep when you
			wanted to? (B)
			Over the last month, how well
			could you sleep through the
			night? (B)
			Last night, how well could you
			fall asleep when you wanted to?
			(B)
			Last night, how well could you
			sleep through the night? (B)
	Diet	Diet quality	Over the last month, how
			healthy was your overall diet?
			(B)
		Food load	When did you last eat or drink	hours
		(time since	anything (other than water)? (B)
		food)
		Intervention	Fasting, vegan, paleo
	Sun exposure	Sun	Over the last week, about how	hours
		exposure	many hours did you spend
		load	outdoors, in direct sunlight?
	Sex drive
Interventions	Vaccines		Have you had any vaccines in
			the past three months? Please
			select all that apply (B)
	Treatment	Treatment
		“Special”	We encourage you to share
		Prescriptions	treatments on your profile. If
		drugs	you are taking any prescription
			drugs to manage your disease
			but are NOT comfortable
			showing them in your profile,
			please select them: (B)
	Procedures
	Supplement
Systems	Circulatory
	Dental
	Digestive
	Endocrine
	Lymph/Immune
	Metabolism			sugar, insulin,
				glucagon, IR, . . .
	Musculoskeletal
	Nervous
	(including
	brain)
	Renal
	Reproductive			including: pregnancy
	(history and			duration,
	current)			breastfeeding, pre x
				post menopause, pre
				menopausal: with
				menstrual periods x
				without)
	Respiratory
	Skin
Environmental	Life events
	including
	trauma
	Living
	environment
	Work
	Chemical
	exposures
	Social
	functioning
Conditions	Diagnostic	Diagnosed	When were you diagnosed	e.g., onset of
	history	by HCP	with <condition> by a	symptoms, diagnosis
			healthcare provider?	date, second
				opinions
		Diagnosis
		prediction
		Onset of
		symptoms
		Diagnosed
		date
		Second
		opinion
		Diagnostic
		labs and tests
		Diagnosis
		confidence
		index
		PRO score
	Disease	Severity
	severity	index
	Symptoms
	and Signs
	Potential
	complications
	and
	comorbidities
	Monitoring
	labs and tests
	Treatment
	(current and
	history)

Metabolite Detection Techniques

Metabolites in a specimen can be determined using various molecular detection techniques such as mass spectrometry, nuclear magnetic resonance, chromatography, or other methods. Oftentimes, mass spectrometry is used in combination with a chromatography technique in order to separate metabolites of interest prior to mass spectrometry analysis in order to provide enhanced sensitivity of detection and/or quantitation of metabolites in complex samples. For example, high performance liquid chromatography (HPLC), gas chromatography (GC), and capillary electrophoresis (CE) may be coupled to mass spectrometric analysis to evaluate metabolites in a biological sample.

A cohort sample set can be processed in sample groups with subject samples and pooled plasma samples for QC/normalization purposes. Each sample group is then analyzed on the LC-MS platform shortly after processing, for example the day following the completion of sample processing. Consistent with the specification, alternative numbers of subject and normalization samples are employed in certain examples.

In some cases, LC-MS data from each sample is collected on an appropriate instrument with an appropriate ionization source, for example a quadrupole time-of-flight (Q-TOF) mass spectrometer coupled to ultra-high performance liquid chromatography (UHPLC) instrument, with an electrospray ionization (ESI) source. LC flow rates can be optimized based on sample conditions and pressures.

The biological sample can be assessed by analysis of a number of injections from a single pooled source. For example, a collection of blood samples is assessed by LC-MS using multiple injections from a single pooled source. Data is collected in MS1/MS2 mode so that feature identifications can be made concurrently with the quantitative MSI data. Tandem mass spectrometry data is collected via a second fragmentation method, such as collision induced dissociation (CID), in which an MSI survey scan is followed by fragmentation of other precursor ions, such as the three most abundant precursor ions.

Algorithms

Disclosed herein are algorithms for analyzing input data for one or more biomarkers to generate output relating to differential classifications or associations such as the presence or likelihood of a disease, disorder, or condition or trait. In some embodiments, the input data comprises one or more data types such as metabolite data, genetic data, protein data, or any combination thereof. Analyses of input data such as metabolite data, and the differential classifications derived therefrom are typically performed using various algorithms and programs. The levels of individual metabolites can make up a metabolite pattern, signature, or profile that corresponds to a particular individual. The machine learning algorithms described herein can generate classifications that account for the complex interrelationships between different metabolites and the pathways that impact those metabolites. Metabolite signatures can provide insight into the health status and/or therapeutic options for the individual. In some embodiments, non-metabolite data such as gene expression data and/or protein quantification data is analyzed alone or in combination with each or with metabolite data using any of the algorithms or methods described herein. Accordingly, genetic signatures and/or protein signatures can also provide insight into the health status or other traits for the individual. In some cases, the algorithms disclosed herein allow for detection, evaluation, assessment, and/or diagnosis of two or more diseases, disorders, or conditions or traits. The two or more diseases, disorders, or conditions or traits may be related, for example, falling within a common category such as autoimmune disorder or immune-related disorder. In some cases, diseases, disorders, or conditions or traits are related if they share one or more common features that are predictive of their status such as in the case of overlapping feature sets of biomarker panels.

Metabolites displaying differential signaling patterns, i.e., discriminating metabolites, between samples obtained from reference subjects (e.g., healthy subjects or subjects with a different disease) can be identified using known statistical tests such as a Student's T-test or ANOVA. The statistical analyses can be applied to select the discriminating metabolites that distinguish the different conditions at predetermined stringency levels. In some cases, metabolites are evaluated for feature importance within one or more models such as shown in FIG. 15B. In some embodiments, a list of the most discriminating metabolites can be obtained by ranking the metabolites by statistical means such as their feature importance. For example, discriminating metabolites can be ranked and identified as having feature importance of between zero and one hundred. In some instances, the cutoff feature importance value for determining the discriminating metabolite can be adjusted to at least 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or 95 (out of 100) for one or more models. Such statistical tests disclosed herein can also be applied to non-metabolite features such as genes and proteins that provide differential patterns between cohorts of subjects such as healthy and sick cohorts.

In some cases, a metabolite biomarker panel as used herein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 of the metabolites listed in FIG. 15A. In some cases, a metabolite biomarker panel as used herein comprises no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 of the metabolites listed in FIG. 15A. In some cases, a metabolite biomarker panel as used herein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or 26 of the metabolites listed in FIG. 17A. In some cases, a metabolite biomarker panel as used herein comprises no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or 26 of the metabolites listed in FIG. 17A. The biomarker panel may be suitable for classifying or evaluating multiple sclerosis (MS) and/or a related or similar disease, disorder, or condition.

In some cases, a metabolite biomarker panel as used herein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 of the metabolites listed in FIG. 22A. In some cases, a metabolite biomarker panel as used herein comprises no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 of the metabolites listed in FIG. 22A. In some cases, a metabolite biomarker panel as used herein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 of the metabolites listed in FIG. 24A. In some cases, a metabolite biomarker panel as used herein comprises no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 of the metabolites listed in FIG. 24A. The biomarker panel may be suitable for classifying or evaluating amyotrophic lateral sclerosis (ALS) and/or a related or similar disease, disorder, or condition.

In some cases, a metabolite biomarker panel as used herein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 of the metabolites listed in FIG. 27A. In some cases, a metabolite biomarker panel as used herein comprises no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 of the metabolites listed in FIG. 27A. In some cases, a metabolite biomarker panel as used herein comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 of the metabolites listed in FIG. 29A. In some cases, a metabolite biomarker panel as used herein comprises no more than 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, or 24 of the metabolites listed in FIG. 29A. The biomarker panel may be suitable for classifying or evaluating systemic lupus erythematosus (SLE) and/or a related or similar disease, disorder, or condition.

In some instances, the systems, media, and methods disclosed herein apply machine learning models or algorithms that use one or more biomarker panels to identify, classify, evaluate, or differentiate between related diseases, disorders, or conditions. Related diseases, disorders, or conditions can include autoimmune or immune-related diseases, disorders, or conditions. In some cases, the systems, media, and methods disclosed herein comprise monitoring or evaluating biomarkers such as metabolites for an individual over time (optionally with or without treatment) and generating a recommendation for a treatment.

In some cases, information of the discriminating metabolites selected can be subsequently imported into a machine learning algorithm to obtain a statistical or mathematical model (e.g., a classifier) that classifies the metabolic data with accuracy, sensitivity, and/or specificity. Any one of the many computational algorithms can be utilized for the classification purposes. Likewise, information for discriminating genes or proteins can also be imported into a machine learning algorithm to generate a model that classifies data or generates a risk prediction based on the data including metabolic data, gene expression data, protein quantification data, or any combination thereof.

The classifiers can be rule-based or machine learning algorithms. The machine learning classification algorithms can be supervised or unsupervised. A basic classification algorithm, Linear Discriminant Analysis (LDA) may be used in analyzing biomedical data in order to classify two or more disease classes. LDA can be, for example, a classification algorithm. A more complex classification method, Support Vector Machines (SVM), uses mathematical kernels to project the original predictors to higher-dimensional spaces, then identifies the hyperplane that optimally separates the samples according to their class. Some common kernels include linear, polynomial, sigmoid or radial basis functions. Other algorithms for data analysis and predictive modeling based on metabolite data can include but are not limited to Naive Bayes Classifiers, Logistic Regression, Quadratic Discriminant Analysis, K-Nearest Neighbors (KNN), K Star, Attribute Selected Classifier (ACS), Classification via clustering, Classification via Regression, Hyper Pipes, Voting Feature Interval Classifier, Decision Trees, Random Forest, and Neural Networks, including Deep Learning approaches.

In some embodiments, a machine learning algorithm (or software module) of a platform or system as described herein utilizes one or more neural networks. A neural network is a type of computational system that can learn the relationships between an input data set and a target data set. A neural network is a software representation of a human neural system (e.g., cognitive system), intended to capture “learning” and “generalization” abilities as used by a human. In some embodiments machine learning algorithm (or software module), the machine learning algorithm (or software module) comprises a neural network comprising a convolutional neural network. Non-limiting examples of structural components of embodiments of the machine learning software described herein include: convolutional neural networks, recurrent neural networks, dilated convolutional neural networks, fully connected neural networks, deep generative models, and Boltzmann machines.

In some embodiments, a neural network is comprised of a series of layers termed “neurons.” In some embodiments, a neural networks comprises an input layer, to which data is presented; one or more internal, and/or “hidden,” layers; and an output layer. A neuron may be connected to neurons in other layers via connections that have weights, which are parameters that control the strength of the connection. The number of neurons in each layer may be related to the complexity of the problem to be solved. The minimum number of neurons required in a layer may be determined by the problem complexity, and the maximum number may be limited by the ability of the neural network to generalize. The input neurons may receive data from data being presented and then transmit that data to the first hidden layer through connections' weights, which are modified during training. The first hidden layer may process the data and transmit its result to the next layer through a second set of weighted connections. Each subsequent layer may “pool” the results from the previous layers into more complex relationships. In addition, whereas conventional software programs require writing specific instructions to perform a function, neural networks are programmed by training them with a known sample set and allowing them to modify themselves during (and after) training so as to provide a desired output such as an output value. After training, when a neural network is presented with new input data, it is configured to generalize what was “learned” during training and apply what was learned from training to the new previously unseen input data in order to generate an output associated with that input.

In some embodiments, metabolite profiles are obtained from a training set of samples, which are used to identify the most discriminative combination of metabolites. In some cases, the most discriminative combination of metabolites is identified by applying an elimination algorithm based on SVM analysis. The accuracy of the algorithm using various numbers of input metabolites ranked by level of statistical significance can be determined by cross-validation. To generate and evaluate metabolite profiles of a feasible number of discriminating metabolites, multiple models can be built using a plurality of discriminating metabolites to identify the best performing model(s). In some cases, an Ensemble model is generated that incorporates a plurality of models. The Ensemble model can provide classification of samples that is subject to less variation than individual models or classifiers that are incorporated into the Ensemble model.

In some instances, specific metabolite(s) are excluded from inclusion in the training and/or testing of machine learning algorithms. Metabolites can be excluded based on certain rules designed to reduce sample-to-sample variation. For example, certain metabolites undergo significant variation over time and may correspond to certain activities such as, for example, consumption of food or liquids, physical activity, sleep, or other factors. Accordingly, failure to account for these factors can result in considerable variation of corresponding metabolites that consequently reduce the predictive performance of classifiers trained using data for these metabolites. Thus, in some cases, the methods described herein comprise removing or excluding one or more metabolites from inclusion in the classifier(s) in order to enhance predictive performance. In some embodiments, a feature list or panel of features (e.g., biomarkers) comprises at least 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000, 2000, 3000, 4000, 5000, 10000, 20000, 30000, 40000, or 50000 metabolites and/or no more than 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1000, 2000, 3000, 4000, 5000, 10000, 20000, 30000, 40000, or 50000 metabolites that are used in a specific machine learning algorithm or classifier.

Multiple models comprising different numbers of discriminating metabolites can be generated, and the performance of each model can be evaluated by a cross-validation process. An SVM classifier can be trained and cross-validated by assigning each sample of a training set of samples to one of a plurality of cross-validation groups. For example, for a five-fold cross-validation, each sample is assigned to one of four cross-validation groups such that each group comprises test and control or reference samples. One of the cross-validation groups is held-out, and a classifier model is trained using the samples in the remaining groups 2-4. Metabolites that discriminate test cases and reference samples in the training group can be analyzed and ranked, for example by statistical p-value. The top k metabolites can be used as predictors for the model. To evaluate the relationship between the number of input predictors and model performance, and to guard against overfitting, the sub-loop is repeated for a range of k such as 10, 25, 50 top metabolites or more. Predictions or classification of samples in group 1 are made using the model generated using groups 2-4. Models for each of the four groups are generated, and the performance (AUC, sensitivity and/or specificity) can be calculated using all the predictions from the 4 models using data from true disease samples. The cross-validation steps can be repeated at least 100 times, and the average performance is calculated relative to a confidence interval such as, for example, 95%.

Alternatively, unsupervised learning can be used to train a classifier or model without using labeled cases or samples. A common example of unsupervised training entails cluster analysis. Non-limiting examples of clustering algorithms include hierarchical clustering, k-means clustering, Gaussian mixture models, and Hidden Markov models.

In some cases, a plurality of machine learning algorithms are utilized to generate a final Ensemble model. The plurality of machine learning algorithms can comprise two or more of: Generalized Linear Model (glmnet), Random Forests (if), Partial Least Squares (pls), Extreme Gradient Boosting (xgbDART), Support Vector Machines with Linear Basis Function Kernel (svmLinear), Support Vector Machines with Radial Basis Function Kernel (svmRadial), or Neural Networks (nnet). Two or more of these 7 algorithms can be run with various different random seed train/test splits.

The classifier used to generate predictions includes one or more selected feature spaces such as metabolite, gene expression, protein quantity, or any combination thereof. The values for these features obtained from a sample can be fed into the classifier or trained algorithm to generate one or more predictions. In some cases, the methods disclosed herein select for the variables that are of predictive value, for example, by culling the features to generate a feature subset used for generating predictions in the final classifier or model. Methods that reduce the number of variables or features can be selected from a non-limiting group of algorithms including principal component analysis (PCA), partial least squares (PLS) regression, and independent component analysis (ICA). In some cases, the methods disclosed herein analyze numerous variables directly and are selected from a non-limiting group of algorithms including methods based on machine learning processes. Machine learning processes can include random forest algorithms, bagging techniques, boosting methods, or any combination thereof. Methods may be statistical methods. Statistical methods can include penalized logistic regression, prediction analysis of microarrays, methods based on shrunken centroids, support vector machine analysis, or regularized linear discriminant analysis.

A feature space can comprise a panel of metabolites, genes, proteins, or any combination thereof within a sample. In some cases, the classifier or trained algorithm comprises a metabolite panel comprising at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, or at least 50 or more metabolites (e.g., metabolite levels). In some cases, the classifier or trained algorithm comprises a genetic panel comprising at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, or at least 50 or more genes (e.g., gene expression levels). In some cases, the classifier or trained algorithm comprises a protein panel comprising at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, or at least 50 or more proteins (e.g., protein levels).

An optimal model/classifier based on metabolite data can be selected and used to classify a test set. The performance of different classifiers is determined using a validation set and/or using a test set of samples. Accordingly, performance characteristics such as accuracy, sensitivity, specificity, and Area Under the Curve (AUC) of the Receiver Operating Characteristic (AUC) curve can be obtained from a given model. In some embodiments, different sets of discriminating metabolites are identified to distinguish different diseases, disorders, or conditions. Accordingly, an optimal model/classifier based on a set of the most discriminating input metabolites is established for each of the diseases, disorders, or conditions to provide a differential diagnosis.

In some instances, a plurality of models is combined or consolidated into an Ensemble classifier or model. The plurality of models can include two, three, four, five, six, seven, or more models. In some cases, the Ensemble model is an average of the plurality of models. One challenge that can arise in the classification of a particular disease, disorder, or condition is that some such diseases, disorders, or conditions are closely related and may share one or more common features used to train the classifier or model. For example, FIG. 13A shows the AUC curve for multiple sclerosis, and the model generates false positive multiple sclerosis calls that misclassify a substantial number of amyotrophic lupus erythematosus positive cases (i.e., ALS positive cases are mistaken for MS positive cases by the MS classifier). Thus, a classification approach that incorporates both MS and ALS models may be able to more accurately detect MS and ALS, respectively, than individual models alone. For example, application of a single model for detection of a single disease, disorder or condition may provide a positive or negative assessment as to the presence of the disease, disorder, or condition, but a patient who has a related but different disorder may be identified as a false positive since the model is not configured to account for this scenario. By applying multiple models directed to related diseases, disorders, or conditions, a false positive for one disorder may be converted into a true positive for another disorder. This information can be used to facilitate downstream steps such as further testing to confirm the identified disorder and/or to provide treatment. Accordingly, in some aspects, the methods described herein incorporate a plurality of models configured to generate a plurality of related classifications. The plurality of related classifications can include MS, ALS, SLE, or any combination thereof. In some cases, the plurality of related classifications include neurodegenerative diseases. The plurality of related classifications can comprise classifications that share one or more discriminating metabolites (e.g., model features) such as, for example, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 metabolites.

Systems for Classifying an Individual

In some aspects, a system as described herein is configured to generate a classification of an individual relative to one or more related classifications. The system as described herein can comprise a network element for communicating with a server. Sometimes, the system comprises a server. The system can be configured to upload to and/or download data from the server. In some cases, the server is configured to store metabolite data and/or other information for the subject. The server can be configured to store historical data (e.g., past metabolite data) for the subject. In some instances, the server is configured to backup data from the system. In certain cases, the system is configured to perform any of the methods described herein.

In some aspects, a system as described herein is configured to generate a classification of an individual for one or more diseases, disorders, or conditions. The system can comprise a network element communicating with a server on a network and a device, the device comprising: a processor; and a non-transitory computer-readable medium including instructions executable by the processor and configured to cause the processor to: (a) receiving data relating to a specimen taken from the individual; (b) providing the data as input to one or more machine learning algorithms; and (c) generating, using the one or more machine learning algorithms, a classification of the individual relative to a plurality of related classifications based on the data.

In some cases, the system is configured to encrypt data. In some embodiments, data on the server is encrypted. The system or apparatus can comprise a data storage unit or memory for storing data. In certain instances, data encryption is carried out using Advanced Encryption Standard (AES). Data encryption is often carried out using 128-bit or 256-bit AES encryption. Data encryption can include full-disk encryption of the data storage unit. In some instances, data encryption comprises virtual disk encryption (e.g., encrypting a folder containing sensor data files for a subject). In various aspects, data encryption comprises file encryption (e.g., encrypting sensor data files for an individual). Sometimes, data that is transmitted or otherwise communicated between the system or apparatus and other devices or servers is encrypted during transit. Wireless communications between the system and other devices or servers can be encrypted. Data in transit can be encrypted using a Secure Sockets Layer (SSL).

A system as described herein can comprise a digital processing device that includes one or more hardware central processing units (CPUs) or general purpose graphics processing units (GPGPUs) that carry out the device's functions. The digital processing device further comprises an operating system configured to perform executable instructions. The digital processing device is optionally connected to a computer network. The digital processing device is optionally connected to the Internet such that it accesses the World Wide Web. The digital processing device is optionally connected to a cloud computing infrastructure. Suitable digital processing devices include, by way of non-limiting examples, server computers, desktop computers, laptop computers, notebook computers, sub-notebook computers, netbook computers, netpad computers, set-top computers, media streaming devices, handheld computers, Internet appliances, mobile smartphones, tablet computers, personal digital assistants, video game consoles, and vehicles. Those of skill in the art will recognize that many smartphones are suitable for use in the system described herein.

Typically, a digital processing device includes an operating system configured to perform executable instructions. The operating system is, for example, software, including programs and data, which manages the device's hardware and provides services for execution of applications. Those of skill in the art will recognize that suitable server operating systems include, by way of non-limiting examples, FreeBSD, OpenBSD, NetBSD®, Linux, Apple® Mac OS X Server®, Oracle® Solaris®, Windows Server®, and Novell® NetWare®. Those of skill in the art will recognize that suitable personal computer operating systems include, by way of non-limiting examples, Microsoft® Windows®, Apple® Mac OS X®, UNIX®, and UNIX-like operating systems such as GNU/Linux®. In some embodiments, the operating system is provided by cloud computing.

A digital processing device as described herein either includes or is operatively coupled to a storage and/or memory device. The storage and/or memory device is one or more physical apparatuses used to store data or programs on a temporary or permanent basis. In some embodiments, the device is volatile memory and requires power to maintain stored information. In some embodiments, the device is non-volatile memory and retains stored information when the digital processing device is not powered. In further embodiments, the non-volatile memory comprises flash memory. In some embodiments, the non-volatile memory comprises dynamic random-access memory (DRAM). In some embodiments, the non-volatile memory comprises ferroelectric random access memory (FRAM). In some embodiments, the non-volatile memory comprises phase-change random access memory (PRAM). In other embodiments, the device is a storage device including, by way of non-limiting examples, CD-ROMs, DVDs, flash memory devices, magnetic disk drives, magnetic tapes drives, optical disk drives, and cloud computing based storage. In further embodiments, the storage and/or memory device is a combination of devices such as those disclosed herein.

A system or method as described herein can be used to generate a classification based on data such as metabolite data which may then be used to determine whether an individual has or is at risk of having a disease, disorder, or condition. In addition, in some embodiments, a system or method as described herein generates a database as containing or comprising past and/or present metabolite data and/or classifications.

Some embodiments of the systems described herein are computer based systems. These embodiments include a CPU including a processor and memory which may be in the form of a non-transitory computer-readable storage medium. These system embodiments further include software that is typically stored in memory (such as in the form of a non-transitory computer-readable storage medium) where the software is configured to cause the processor to carry out a function. Software embodiments incorporated into the systems described herein contain one or more modules.

In various embodiments, an apparatus comprises a computing device or component such as a digital processing device. In some of the embodiments described herein, a digital processing device includes a display to send visual information to a user. Non-limiting examples of displays suitable for use with the systems and methods described herein include a liquid crystal display (LCD), a thin film transistor liquid crystal display (TFT-LCD), an organic light emitting diode (OLED) display, an OLED display, an active-matrix OLED (AMOLED) display, or a plasma display.

A digital processing device, in some of the embodiments described herein includes an input device to receive information from a user. Non-limiting examples of input devices suitable for use with the systems and methods described herein include a keyboard, a mouse, trackball, track pad, or stylus. In some embodiments, the input device is a touch screen or a multi-touch screen.

The systems and methods described herein typically include one or more non-transitory computer-readable storage media encoded with a program including instructions executable by the operating system of an optionally networked digital processing device. In some embodiments of the systems and methods described herein, the non-transitory storage medium is a component of a digital processing device that is a component of a system or is utilized in a method. In still further embodiments, a computer-readable storage medium is optionally removable from a digital processing device. In some embodiments, a computer-readable storage medium includes, by way of non-limiting examples, CD-ROMs, DVDs, flash memory devices, solid state memory, magnetic disk drives, magnetic tape drives, optical disk drives, cloud computing systems and services, and the like. In some cases, the program and instructions are permanently, substantially permanently, semi-permanently, or non-transitorily encoded on the media.

Typically the systems and methods described herein include at least one computer program, or use of the same. A computer program includes a sequence of instructions, executable in the digital processing device's CPU, written to perform a specified task. Computer-readable instructions may be implemented as program modules, such as functions, objects, Application Programming Interfaces (APIs), data structures, and the like, that perform particular tasks or implement particular abstract data types. In light of the disclosure provided herein, those of skill in the art will recognize that a computer program may be written in various versions of various languages. The functionality of the computer-readable instructions may be combined or distributed as desired in various environments. In some embodiments, a computer program comprises one sequence of instructions. In some embodiments, a computer program comprises a plurality of sequences of instructions. In some embodiments, a computer program is provided from one location. In other embodiments, a computer program is provided from a plurality of locations. In various embodiments, a computer program includes one or more software modules. In various embodiments, a computer program includes, in part or in whole, one or more web applications, one or more mobile applications, one or more standalone applications, one or more web browser plug-ins, extensions, add-ins, or add-ons, or combinations thereof. In various embodiments, a software module comprises a file, a section of code, a programming object, a programming structure, or combinations thereof. In further various embodiments, a software module comprises a plurality of files, a plurality of sections of code, a plurality of programming objects, a plurality of programming structures, or combinations thereof. In various embodiments, the one or more software modules comprise, by way of non-limiting examples, a web application, a mobile application, and a standalone application. In some embodiments, software modules are in one computer program or application. In other embodiments, software modules are in more than one computer program or application. In some embodiments, software modules are hosted on one machine. In other embodiments, software modules are hosted on more than one machine. In further embodiments, software modules are hosted on cloud computing platforms. In some embodiments, software modules are hosted on one or more machines in one location. In other embodiments, software modules are hosted on one or more machines in more than one location.

Typically, the systems and methods described herein include and/or utilize one or more databases. In view of the disclosure provided herein, those of skill in the art will recognize that many databases are suitable for storage and retrieval of baseline datasets, files, file systems, objects, systems of objects, as well as data structures and other types of information described herein. In various embodiments, suitable databases include, by way of non-limiting examples, relational databases, non-relational databases, object oriented databases, object databases, entity-relationship model databases, associative databases, and XML databases. Further non-limiting examples include SQL, PostgreSQL, MySQL, Oracle, DB2, and Sybase. In some embodiments, a database is internet-based. In further embodiments, a database is web-based. In still further embodiments, a database is cloud computing-based. In other embodiments, a database is based on one or more local computer storage devices.

FIG. 32 shows an exemplary embodiment of a system as described herein comprising an apparatus such as a digital processing device 3201. The digital processing device 3201 includes a software application configured to generate a classification of an individual by, for example, analyzing data using a machine learning classifier. The digital processing device 3201 may include a central processing unit (CPU, also “processor” and “computer processor” herein) 3205, which can be a single core or multi-core processor, or a plurality of processors for parallel processing. The digital processing device 3201 also includes either memory or a memory location 3210 (e.g., random-access memory, read-only memory, flash memory), electronic storage unit 3215 (e.g., hard disk), communication interface 3220 (e.g., network adapter, network interface) for communicating with one or more other systems, and peripheral devices, such as cache. The peripheral devices can include storage device(s) or storage medium 3265 which communicate with the rest of the device via a storage interface 3270. The memory 3210, storage unit 3215, interface 3220 and peripheral devices are configured to communicate with the CPU 3205 through a communication bus 3225, such as a motherboard. The digital processing device 3201 can be operatively coupled to a computer network (“network”) 3230 with the aid of the communication interface 3220. The network 3230 can comprise the Internet. The network 3230 can be a telecommunication and/or data network.

The digital processing device 3201 includes input device(s) 3245 to receive information from a user, the input device(s) in communication with other elements of the device via an input interface 3250. The digital processing device 3201 can include output device(s) 3255 that communicates to other elements of the device via an output interface 3260.

The CPU 3205 is configured to execute machine-readable instructions embodied in a software application or module. The instructions may be stored in a memory location, such as the memory 3210. The memory 3210 may include various components (e.g., machine readable media) including, but not limited to, a random access memory component (e.g., RAM) (e.g., a static RAM “SRAM”, a dynamic RAM “DRAM, etc.), or a read-only component (e.g., ROM). The memory 3210 can also include a basic input/output system (BIOS), including basic routines that help to transfer information between elements within the digital processing device, such as during device start-up, may be stored in the memory 3210.

The storage unit 3215 can be configured to store files, such as patient information, e.g., metabolite data and non-molecular data. The storage unit 3215 can also be used to store operating system, application programs, and the like. Optionally, storage unit 3215 may be removably interfaced with the digital processing device (e.g., via an external port connector (not shown)) and/or via a storage unit interface. Software may reside, completely or partially, within a computer-readable storage medium within or outside of the storage unit 3215. In another example, software may reside, completely or partially, within processor(s) 3205.

Information and data can be displayed to a user through a display 3235. The display is connected to the bus 3225 via an interface 3240, and transport of data between the display other elements of the device 3201 can be controlled via the interface 3240.

Methods as described herein can be implemented by way of machine (e.g., computer processor) executable code stored on an electronic storage location of the digital processing device 3201, such as, for example, on the memory 3210 or electronic storage unit 3215. The machine executable or machine readable code can be provided in the form of a software application or software module. During use, the code can be executed by the processor 3205. In some cases, the code can be retrieved from the storage unit 3215 and stored on the memory 3210 for ready access by the processor 3205. In some situations, the electronic storage unit 3215 can be precluded, and machine-executable instructions are stored on memory 3210.

In some embodiments, a remote device 3202 is configured to communicate with the digital processing device 3201, and may comprise any mobile computing device, non-limiting examples of which include a tablet computer, laptop computer, smartphone, or smartwatch. For example, in some embodiments, the remote device 3202 is a smartphone of the user that is configured to receive information from the digital processing device 3201 of the apparatus or system described herein in which the information can include a summary, classifications or predictions, or other data. In some embodiments, the remote device 3202 is a server on the network configured to send and/or receive data from the system described herein.

Some embodiments of the systems and methods described herein are configured to generate a database containing or comprising patient information such as metabolite data. A database, as described herein, is configured to function as, for example, a lookup table for healthcare providers, other medical industry professionals and/or other end users. In these embodiments of the systems and methods described herein, metabolite data and/or classifications or diagnoses are presented in a database so that a user is able to, for example, identify whether a specific individual is at risk of certain diseases, disorders, or conditions. In some embodiments, the database is stored on a server on the network. In some embodiments the database is stored locally on the apparatus (e.g., the monitor component of the apparatus). In some embodiments, the database is stored locally with data backup provided by a server.

Certain Terminology

As used herein, the terms “patient,” “individual,” and “subject” encompasses mammals. Examples of mammals include, but are not limited to, any member of the mammalian class: humans, non-human primates such as chimpanzees, and other apes and monkey species; farm animals such as cattle, horses, sheep, goats, swine; domestic animals such as rabbits, dogs, and cats; laboratory animals including rodents, such as rats, mice and guinea pigs, and the like. In one aspect, the mammal is a human. The term “animal” as used herein comprises human beings and non-human animals. In one embodiment, a “non-human animal” is a mammal, for example a rodent such as rat or a mouse.

As used herein, the term “classify” or “classification” refers to the output of the model or algorithm being a categorical output, for example, positive identification of a disease, disorder, or condition. As used herein, the term “regression” refers to the output of the model or algorithm being a non-categorical output, for example, a number or continuous variable. As classification and regression can both fall under supervised machine learning, a regression output is also contemplated wherever classification is described within the present disclosure. Therefore, disclosure of “a classifier” configured to evaluate the status of a disease, disorder, or condition is to be interpreted as also disclosing a regression model or algorithm.

EXAMPLES

Example 1

In some cases, a plurality of machine learning algorithms are utilized to generate a final Ensemble model. The plurality of machine learning algorithms can comprise two or more of: Generalized Linear Model (glmnet), Random Forests (rf), Partial Least Squares (pls), Extreme Gradient Boosting (xgbDART), Support Vector Machines with Linear Basis Function Kernel (svmLinear), Support Vector Machines with Radial Basis Function Kernel (svmRadial), or Neural Networks (nnet). Two or more of these 7 algorithms can be run with various different random seed train/test splits.

For example, 3 different random seed train/test splits were run for all 7 algorithms for 21 models total with respect to MS, ALS, and SLE. Models were run for all conditions with metabolite data for those classifications having more than 35 participants (see FIG. 1). Disease positive samples were run against all negative samples for that specific disease condition. Only models with AUC>0.8 contributed to final participant score. Features were screened for downstream drug metabolites and availability as supplements. Metabolite features were selected by raw p-value>0.1 in Condition vs. Control t-test. The results for MS, ALS, and SLE are shown at least in FIGS. 3-5.

While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

1. A system, comprising: (a) a processor; and(b) a non-transitory computer readable medium tangibly encoded with software comprising a plurality of machine learning algorithms together with instructions configured to cause the processor to: i) receive, via transmission over a network from a server, data related to a specimen taken from an individual, the data indicating the specimen according to a time period, the data received over the network being encrypted during the transmission;ii) consolidate the plurality of machine learning algorithms into an ensemble of machine learning algorithms;iii) provide the data as input to the ensemble of machine learning algorithms;iv) generate, via execution of the ensemble of machine learning algorithms, a classification of the individual relative to a plurality of related classifications by: a. analyzing, via execution of the ensemble of machine learning algorithms, the data provided as input, the analysis comprising identifying at least one trait of the individual identified from the data via the ensemble of machine learning algorithms performing feature selection;b. determining, based on the analysis via the ensemble of machine learning algorithms, at least one biomarker associated with the individual, the at least one biomarker corresponding to the at least one trait;c. analyzing, via further execution of the ensemble of machine learning algorithms, the at least one biomarker, the analysis of the at least one biomarker corresponding to an automated feature selection process based on a set of gene ontology tags;d. determining, based on the analysis of the at least one biomarker via the ensemble of machine learning algorithms, a likelihood of a disease over the time period; ande. generating the classification in accordance with information related to the likelihood determined via an output of the ensemble of machine learning algorithms;v) analyze, via the ensemble of machine learning algorithms, the generated classification;vi) generate, based on the analysis of the generated classification, a displayable evaluation report, the evaluation report comprising functionality for an intuitive visualization of the classification according to the time period, the evaluation report further comprising information related to a treatment for at least one condition associated with the classification; andvii) cause display, on a display of a device, of the evaluation report thereby providing the functionality for the intuitive visualization of the classification, the intuitive visualization providing functionality for tracking and monitoring the individual as the treatment progresses and updating the display of the evaluation report to visibly display an impact of the treatment on the at least one condition, wherein the impact is determined based on further analysis of the generated classification of the identified biomarkers via the ensemble of machine learning algorithms.

2. The system of claim 1, wherein the classification comprises multiple sclerosis, amyotrophic lateral sclerosis, systemic lupus erythematosus, fibromyalgia, gastrointestinal reflux disease, or any combination thereof.

3. The system of claim 1, wherein the ensemble comprises at least three machine learning algorithms.

4. The system of claim 1, wherein the ensemble of machine learning algorithms comprises a Generalized Linear algorithm, a Random Forests algorithm, a Partial Least Squares algorithm, and Extreme Gradient Boosting algorithm, a Support Vector Machines with Linear Basis Function Kernel algorithm, a Support Vector Machines with Radial Basis Function Kernel, and a Neural Networks algorithm.

5. The system of claim 1, wherein each machine learning algorithm of the ensemble of machine learning algorithms produces an output that is averaged by the software.

6. The system of claim 1, wherein each machine learning algorithm of the ensemble of machine learning algorithms produces an output and wherein at least one output is an input for at least one of the machine learning algorithms.

7. The system of claim 1, wherein at least one machine learning algorithm is trained using data relating to specimens from other individuals.

8. The system of claim 1, wherein the specimen comprises a biological sample.

9. The system of claim 1, wherein the specimen comprises at least one of a sputum sample, a urine sample, a blood sample, a cerebrospinal fluid sample, a stool sample, a hair sample, and a biopsy.

10. The system of claim 1, wherein the data relates to a metabolite, a protein, a nucleic acid, or any combination thereof.

11. The system of claim 10, wherein the metabolite comprises at least one of oleamide, creatine, and 4-methyl-2-oxopentanoate.

12. The system of claim 1, wherein the instructions are further configured to cause the processor to receive a parameter related to the individual and wherein the ensemble machine learning algorithms use the parameter together with the data to generate the classification of the individual relative to the plurality of related classifications.

13. The system of claim 12, wherein the parameter comprises at least one of an age, a gender, a race, a weight, a body mass index (BMI), a height, a waist size, a blood pressure, a heart rate, and a temperature.

14. The system of claim 1, wherein the plurality of related classifications comprise a spectrum of severity of a single disease, a spectrum of prognoses of a single disease, or a spectrum of related diseases.

15. The system of claim 14, wherein the spectrum of related diseases comprise a plurality of neurological diseases that share at least one common feature.

16. A computer implemented method comprising: (a) receiving, by a device, data relating to a specimen taken from an individual, the data indicating the specimen according to a time period;(b) consolidating, by the device, a plurality of machine learning algorithms into an ensemble of machine learning algorithms;(c) providing, by the device, the data as input to the ensemble of machine learning algorithms;(d) generating, by the device executing the ensemble of machine learning algorithms, a classification of the individual relative to a plurality of related classifications by: a. analyzing, via execution of the ensemble of machine learning algorithms, the data provided as input, the analysis comprising identifying at least one trait of the individual identified from the data via the ensemble of machine learning algorithms performing feature selection;b. determining, based on the analysis via the ensemble of machine learning algorithms, at least one biomarker associated with the individual, the at least one biomarker corresponding to the at least one trait;c. analyzing, via further execution of the ensemble of machine learning algorithms, the at least one biomarker, the analysis of the at least one biomarker corresponding to an automated feature selection process based on a set of gene ontology tags;d. determining, based on the analysis of the at least one biomarker via the ensemble of machine learning algorithms, a likelihood of a disease over the time period; ande. generating the classification in accordance with information related to the likelihood determined via an output of the ensemble of machine learning algorithms;(e) analyzing, by the device via the ensemble of machine learning algorithms, the generated classification;(f) generating, by the device, based on the analysis of the generated classification, a displayable evaluation report, the evaluation report comprising functionality for an intuitive visualization of the classification according to the time period, the evaluation report further comprising information related to a treatment for at least one condition associated with the classification; and(g) causing display, on a display associated with the device, of the evaluation report thereby providing the functionality for the intuitive visualization of the classification, the intuitive visualization providing functionality for tracking and monitoring the individual as the treatment progresses and updating the display of the evaluation report to visibly display an impact of the treatment on the at least one condition, wherein the impact is determined based on further analysis of the generated classification of the identified biomarkers via the ensemble of machine learning algorithms.

17. A system comprising: (a) a processor; and(b) a non-transitory computer readable medium tangibly encoded with software comprising a plurality of machine learning algorithms together with instructions configured to cause the processor to: i) receive data related to a specimen taken from an individual, the data indicating the specimen according to a time period;ii) consolidate the plurality of machine learning algorithms into an ensemble of machine learning algorithms;iii) provide the data as input to the ensemble of machine learning algorithms;iv) generate, via execution of the ensemble of machine learning algorithms, an assessment of one or more traits of the individual according to the time period by: a. analyzing, via execution of the ensemble of machine learning algorithms, the data provided as input, the analysis comprising identifying the one or more traits of the individual identified from the data via the ensemble of machine learning algorithms performing feature selection;b. determining, based on the analysis via the ensemble of machine learning algorithms, one or more biomarker associated with the individual, the at least one biomarker corresponding to the one or more trait;c. analyzing, via further execution of the ensemble of machine learning algorithms, the at least one biomarker, the analysis of the at least one biomarker corresponding to an automated feature selection process based on a set of gene ontology tags;d. determining, based on the analysis of the at least one biomarker via the ensemble of machine learning algorithms, a likelihood of a disease over the time period; ande. generating the assessment in accordance with information related to the likelihood determined via an output of the ensemble of machine learning algorithms;v) analyze, via the ensemble of machine learning algorithms, the assessment;vi) generate, based on the analysis of the assessment, a displayable evaluation report, the evaluation report comprising functionality for an intuitive visualization of the assessment according to the time period, the evaluation report further comprising information related to a treatment for at least one condition associated with the assessment andvii) cause display, on a display of a device, of the evaluation report thereby providing the functionality for the intuitive visualization of the assessment, the intuitive visualization providing functionality for tracking and monitoring the individual as the treatment progresses and updating the display of the evaluation report to visibly display an impact of the treatment on the at least one condition, wherein the impact is determined based on further analysis of the generated assessment of the identified biomarkers via the ensemble of machine learning algorithms.

18. The system of claim 17, wherein the assessment comprises at least one trait selected from a category that is personal characteristics, general health, mental health, health behaviors, interventions, organ systems, environmental, and conditions.