Patent Application
20240274229
The disclosed embodiments relate to assessing populations in which a variant of interest may have arisen and propagated and discovering historical populations from the pattern of genetic relationships between people.
Although humans are, genetically speaking, almost entirely identical, small differences in human DNA are responsible for some observed variation between individuals. In fact, by comparing these small differences in DNA of individuals, it is possible to detect long chromosome segments suggestive of inheritance from a recent common ancestor, and then use these detected segments to estimate how closely two people are related. The process of identifying segments suggestive of recent common inheritance is known in population genetics literature as an analysis of identity-by-descent (IBD). IBD analysis can be used to predict the familial relationship between any two people (e.g., second cousins) in a population. Learning about population structure from genetic polymorphism data is an important topic in genetics. The most widely used methods in this area are based on modeling variation in allele frequencies. These methods have shed light, for example, on historical patterns of migration in human populations. To take one example of this, prior genetic studies of the United States (US) have helped to elucidate the diversity of recent immigrants in relation to other parts of the world (e.g. Europe, Africa).
Disclosed herein are techniques for characterizing variants of interest. Characterizations can provide insights into the origins, migration patterns, and historical and contemporary geographic locations of populations carrying any variant of interest. Since many variants are associated with a phenotype (e.g., a trait, a disease, or another observable characteristic), learning about a variant's origin and distribution can provide insight into the etiology of the associated phenotype and can be extended to targeting at-risk populations.
In one embodiment, a method for characterizing a variant of interest includes obtaining a DNA dataset from an individual. Genotypes of the individual are determined based on the DNA dataset. A set of reference DNA datasets is accessed. Each reference DNA dataset is associated with a reference individual, and each reference individual is a carrier of a variant at a genetic locus. In some embodiments, a phenotype or haplotype may also be chosen. A cluster includes reference individuals and additional individuals who share Identity-by-Descent (IBD) with the reference individuals is generated. The cluster may be generated based on an IBD affinity between the reference individuals and the additional individuals. In some embodiments, the cluster includes nodes, which represent individuals, and weighted edges, which represent the IBD affinity between individuals. To characterize the variant, the identified cluster is annotated with genealogical data (e.g., birth locations, surnames, ancestral birth locations, residences) based on information about the individuals in the cluster. Statistics of the genealogical data are generated to characterize the variant. Results summarizing the characterization of the variant are generated. If it is determined that the individual shares IBD with the cluster at the genetic locus, a report summarizing the characterization of the variant is provided for display.
In various embodiments, the techniques disclosed herein may additionally be used for predicting assignments of individuals to communities based on obtained genetic information. A DNA dataset is obtained for an individual. Genotypes of the individual are determined based on the DNA dataset. The genotypes are phased to generate haplotypes of the individual, and a subset of haplotypes of the individual are selected. A subset is chosen based on the features of a community of interest. The subset of the haplotypes is inputted into a community-specific model to determine whether the individual is a member of the community. The model is trained using training samples, where each training sample includes a group of haplotypes of a reference individual and a label identifying whether the reference individual belongs to the community. The reference individuals who belong to the community have one or more groups of haplotypes that are representative of the community.
Haplotypes that are representative of the community may be identified by performing an enrichment analysis on haplotypes that are common among individual who are known members of the community. Based on the output of the model, it is determined whether the individual is a member of the community.
The figures depict various embodiments for purposes of illustration only. One skilled in the art will readily recognize from the following discussion that alternative embodiments of the structures and methods illustrated herein may be employed without departing from the principles described herein.
The client devices 110 are one or more computing devices capable of receiving user input as well as transmitting and/or receiving data via a network 120. In one embodiment, a client device 110 is a computer system, such as a desktop or a laptop computer. Alternatively, a client device 110 may be a device having computer functionality, such as a personal digital assistant (PDA), a mobile telephone, a smartphone, or another suitable device. A client device 110 is configured to communicate via the network 120. In one embodiment, a client device 110 executes an application allowing a user of the client device 110 to interact with the computing system 130 via a user interface 115 of the client device. For example, a client device 110 executes a web browser application to enable interaction between the client device 110 and the computing system 130 via the network 120. In another embodiment, the user interface 115 takes the form of a graphical user interface as part of a software application published by the computer system 130 and installed on the user device 110. In yet another embodiment, a client device 110 interacts with the computing system 130 through an application programming interface (API) running on a native operating system of the client device 110, such as IOS® or ANDROID™.
The client devices 110 are configured to communicate via a network 120, which may include any combination of local area and/or wide area networks, using both wired and/or wireless communication systems. In one embodiment, a network 120 uses standard communications technologies and/or protocols. For example, a network 120 includes communication links using technologies such as Ethernet, 802.11, worldwide interoperability for microwave access (WiMAX), 3G, 4G, code division multiple access (CDMA), digital subscriber line (DSL), etc. Examples of networking protocols used for communicating via the network 120 include multiprotocol label switching (MPLS), transmission control protocol/Internet protocol (TCP/IP), hypertext transport protocol (HTTP), simple mail transfer protocol (SMTP), and file transfer protocol (FTP). Data exchanged over a network 120 may be represented using any suitable format, such as hypertext markup language (HTML) or extensible markup language (XML). In some embodiments, all or some of the communication links of a network 120 may be encrypted using any suitable technique or techniques.
Individuals provide DNA samples (or DNA datasets) for analysis of their genetic data. In one embodiment, an individual uses a sample collection kit to provide a DNA sample, e.g., saliva, from which genetic data can be reliably extracted according to DNA processing techniques such as DNA sequencing. DNA extraction service 125 receives the sample and estimates genotypes from the genetic data, for example by extracting the DNA from the sample and identifying genotype values of single nucleotide polymorphisms (SNPs) present within the DNA. The result in this example is a diploid genotype for each SNP site.
The computing system 130 receives the genetic data from DNA extraction service 125 and stores the genetic data in a DNA sample store containing DNA diploid genotypes. In some embodiments, the genetic data stored in the DNA sample store may be associated with a user in the user data store via one or more pointers.
The computing system 130 processes the DNA to identify shared IBD between pairs of individuals, and uses that information to identify clusters in a sample of individuals. In one embodiment, a cluster includes individuals in a sample that exhibit a higher density of IBD connections between each other relative to other individuals in the sample. The clusters can be annotated with information about phenotypes characteristic and genealogical data of individuals within the group, and used to develop models that allow assignment of, often new, individuals to those clusters.
The computing system 130 maintains user data in the user data store 205. The store data store 205 maintains user data for each user of the computing system 130. The amount and type of data stored for each user in the user store 205 may vary based on the information provided by the corresponding user. Users may provide data via the user interface 115 of a user device 110. For example, the user may be prompted in an element of a user interface to answer questions related to the user that can be processed to obtain genealogical and survey data. Examples of genealogical data includes names (first, last, middle, suffixes), birth locations, date of birth, date of death, marriage information, kinships, family history, and the like. In some instances, family history can take the form of a pedigree of that individual (e.g., the recorded relationships in the family). The pedigree information associated with a user comprises one or more specified nodes. Each specified node in the pedigree represents either the individuals themselves or an ancestor of the individual corresponding to a stored DNA sample. Therefore, the nodes represent pedigree members that are either the individual themselves, or individuals that could have passed down genetic material to the associated individual. Genealogical data may also include genetic connections among users of the computing system 130. Examples of survey data include information about an individual's phenotypes, such as physical traits (e.g., height, hair, skin pigmentation, freckling, bitter taste, earlobe type, iris patterns, male pattern baldness, hair curl), wellness phenotypes (e.g., lactose tolerance, caffeine consumption, malaria resistance, norovirus resistance, muscle performance, alcohol flush), and personal preferences (e.g., likes and dislikes). The user data store 205 may also include information inferred from the DNA samples stored in the DNA store 210 and information received from the individuals. For example, information related to which individuals are genetically related, how they are related, how many generations back do they share common ancestors, percent IBD shared, which communities the individual is a part of, variants the individual carries, and the like.
The user data store 205 also includes genotypes of the individual generated from the DNA samples. Genotypes may be generated by the sample processing engine 220 or a third-party service. The user data store 205 may also include haplotypes of the individual. Haplotypes are generated by phasing the genotypes. In one embodiment, the user data store 205 contains information about known variants the corresponding individual is a carrier of (e.g., the type of variant, location of the variant, phenotypes associated with the variant). This information can be obtained from the computing system 130, a third-party database or obtained using a third-party software.
The computing system 130 maintains DNA samples of individuals in the DNA sample store 210. DNA samples may contain whole or portions of individual's DNA and corresponding metadata. The data stored in the DNA sample store 210 may store one or more DNA samples linked to a user. In various embodiments, the DNA sample store 210 stores a pointer to a location associated with the user data store 205 associated with the individual.
The sample processing engine 220 receives, processes, and stores data received from an individual via the user interface 115 of the user device 110 or the DNA extraction service 125. To collect the user data (e.g., genealogical and survey data), the sample processing engine may be configured to provide an interactive user interface on the user device 110 that provides interface elements in which users can provide genealogical data and survey data. These data may be manually provided or automatically extracted via, for example, optical character recognition (OCR) performed on census records, town or government records, or any other item of printed or online material.
To collect DNA samples, the sample processing engine 220 is configured to receive DNA samples via the DNA extraction service 125 or sample data from third party sources. The sample processing engine 220 may send the DNA samples to the DNA sample store 210 and to the phasing engine 225. The sample processing engine 220 identifies autosomal SNPs so that the individual's diploid genotype on autosomal chromosomes can be computationally phased. For example, for one individual 700,000 autosomal SNPs may be identified to estimate genotype phase. The sample processing engine 220 provides the identified SNPs to the phasing engine 225 which phases the individual's diploid genotype based on the set of identified SNPs to generate a set of haplotypes for each user.
The phasing engine 225 phases DNA samples so that an individual's haplotypes may be used by the IBD estimation engine 230, variant origination engine 235, and community prediction engine 240. The sets of haplotypes are used by the variant origination engine 235 to characterize variants of interest. The sets of haplotypes are also used by the community prediction engine 240 to determine an individual's membership in a community. The phasing engine 225 generates a pair of estimated haplotypes for each diploid genotype. The estimated haplotypes are stored in the user data store 205 and IBD network store 215. The phasing engine 225 stores phased genotypes in the user data store 205. For phasing a set of genotypes to generate two datasets of haplotype, U.S. patent application Ser. No. 15/591,099, entitled “Haplotype Phasing Models,” filed Oct. 19, 2015 is incorporated by reference for all purposes.
The IBD estimation engine 230 estimates IBD segments from phased genotype data (haplotypes) between pairs of individuals stored in the user data store 205. IBD segments are chromosome segments identified in a pair of individuals that are putatively inherited from a recent common ancestor. Typically, individuals who are closely related share a relatively large number of IBD segments, and the IBD segments tend to have greater length (individually or in aggregate across one or more chromosomes), while individuals who are more distantly related share relatively few IBD segments, and these segments tend to be shorter (individually or in aggregate across one or more chromosomes). For example, while close family members often share upwards of 71 cM of IBD (e.g., third cousins), more distantly related individuals may share less than 12 cM of IBD. The extent of relatedness in terms of IBD segments between two individuals may be referred to as IBD affinity.
IBD estimates are used to build IBD networks that identify individuals who share IBD genome wide and/or IBD at genetic loci. The variant origination engine 235 and the community prediction engine 240 use these networks to identify individuals who are carriers of particular variants and individuals who are a part of a genetic community.
In some embodiments, the IBD network may be used to construct data sets, referred to as reference panels, which can be used to train models. These models can in turn be used to generate a prediction regarding which clusters are relevant to a hypothetical user, such as a new user, based on a sample of their DNA. For example, a cluster may include individuals that are carriers of a particular variant, individuals who are a part of a community, individuals who share IBD at a genetic locus, etc. For more details on clustering and generation of reference panels, US Patent Publication No. US2016/0350479, entitled “Discovering Population Structure from Patterns of Identity-By-Descent,” is hereby incorporated by reference for all purposes.
The variant origination engine 235 characterizes the origination of a variant. The characterization of a variant can provide insights into the origins, migration patterns, and historical and contemporary geographic distributions of populations carrying a variant of interest. Because variants are often associated with a trait, disease, or other phenotype, learning about a variant's origin and distribution may also contribute to the understanding of the etiology associated with the trait, disease, or other phenotype. To do this, the variant origination engine 235 performs an enrichment analysis on the genealogical data of users associated with a variant to identify enriched birth locations during distinct time periods. In some embodiments, users select a set of one or more target variants to characterize. Users may select target variants using interactive interface elements of a user interface 115 on a user device 110. Variant selection may be subject to criteria. Examples of criteria include allele frequency across populations, associated literature or known function, selection pressure, and autosomal or sex-linked inheritance.
The variant origination engine 235 may plot the results of the variant characterization on maps of various geographical locations. The graphical maps and plots described are useful because in various implementations they may be presented to a user via the user interface 115. However, actual generation of the graphical maps and plots is not strictly necessary in order to determine the geographic locations to annotate to a given variant. The description above may be accomplished entirely through non-graphical methods, that is by clustering data based on IBD affinity at the genetic loci of one or more variants of interest, accessing genealogical data of the cluster, and performing statistical analysis on the genealogical data of the cluster to determine the characterization of the variant without presenting results to users on a user interface. In some embodiments, the variant origination engine 235 generates a report of the variant characterization to users that have submitted genotypes and historical family records and have been identified as likely carriers of the variant. For example, the report may include the current and historical distributions, phenotypes associated with the variant, from which family members/ancestors the trait was inherited, years and locations of variant origination, and the like. The report may be presented on a user interface to the individuals in the cluster.
The community prediction engine 240 identifies which communities an individual belongs to using trained community-specific models. Therefore, the training process results in a collection of models that are configured to predict whether or not a given individual belongs to each community. For example, the community prediction engine 240 identifies that each user may be classified into zero, one or more communities. Model training and testing is discussed in detail below.
Once the models have been trained, the community prediction engine 240 can use the models to predict which, if any, communities a new user is a member of based on the new user's genetic sample. The system can use these community predictions to provide a report detailing the individual's predicted community membership without needing to re-build IBD networks or re-train models. In some embodiments, the report includes the binary classifications for the communities the user belongs to. In other embodiments, the report includes the portion of a user's DNA sample that belongs to each community. For example, a report may conclude that a user received 30% of their DNA from an Irish community and 70% of their DNA from a Finnish community. To do this, the amount of overlap between a user's haplotypes and a group of haplotypes representative of a community is used to determine the portion of DNA a user inherited from a particular community.
The IBD estimation engine 230 can partition the IBD network into two or more clusters using various algorithms. Clusters may be generated to identify individuals who share IBD at a genetic locus. For example, IBD sharing at the genetic locus of a variant of interest. Similarly, clusters may be generated to identify individuals who share haplotypes that are representative of a community. For example, IBD sharing at the genetic loci of a set of haplotypes that are only enriched in a particular community
A cluster and community may be used interchangeably in some circumstances. Depending on the granularity, various clusters may represent different genetic communities, such as race and ethnicity groups, migration groups, local ancestors. For an IBD network, the computing system 130 may apply one or more clustering techniques such as K-means, Louvain clustering, etc. to generate one or more clusters of nodes. For example, in one embodiment, clusters in the IBD network are identified by selecting clusters that maximize the modularity objective defined with respect to the IBD network. Clusters identified from a network in this way are often referred to as “communities.” Although modularity-maximizing algorithms may be employed to identify clusters in one or more embodiments, the term “community” is not used in the strict technical sense of a modularity-maximizing clustering, but is instead used more generally to refer to clusters identified in a network by taking any one of several existing network clustering approaches developed in the network analysis or machine learning areas.
Individuals in the network may share IBD genome wide or they may share IBD at a genetic locus. As shown in
Individuals are added to the cluster based on the IBD affinity between the carriers and individuals that was calculated by the IBD estimation engine 230 using the genotypes of the individuals. For example, the genotypes of the e.g., genotypes 405A-D, were used to identify individuals 401A, 401B, 401C, and 401D as nodes of a cluster associated with a variant, e.g., Variant X. In some embodiments, individuals are added to the cluster if the IBD affinity between the corresponding individual and one or more carriers is above a threshold IBD affinity. By identifying additional users who share IBD with carriers, the variant origination engine 235 can characterize the origination of the variant with more statistical confidence than when only known carriers are used to characterize a variant. However, in some embodiments, variants may be characterized using only the data of users who are known carriers of the variant of interest.
The variant origination engine 230 extracts user data such as genealogical data associated with each node in the corresponding cluster (e.g., genealogical data 410A-D), as well as the node's relatives, such as ancestors. Examples of genealogical data may include family history, birth dates, birth locations, residences, dates of death, occupation, political and/or religious beliefs, marriages, and the like. Using this data, the variant origination engine 235 generates statistics to identify enriched birth locations. Statistics to identify enriched birth locations may include an odds ratio and frequency. The odds ratio is defined as the odds that, at a given location, an individual is a carrier of a variant over the odds that the individual is not a carrier of the variant.
The frequency is defined as the fraction of individuals born in a geographic location that carry a variant, trait, haplotype, genotype, etc. of interest (and/or share IBD with individuals that carry the variant of interest) and the total number of individuals born at the geographic location. An enriched birth location may be defined as a set of all rounded latitude-longitude grid points with an odds ratio of at least a threshold (e.g., 5) or with a log frequency of at least a threshold (e.g., 0.9), indicating a geographic location with a relative enrichment of birth locations. In other embodiments, different statistics may be used to identify enriched birth locations. Enrichment analysis may be repeated for different and distinct time periods to characterize the history of the variant. For example, the enrichment analysis for the cluster associated with Variant X identified Detroit, Michigan as an enriched birth location for the cluster during a distinct period of time (e.g., between 1930 A.D and 1960 A.D.). Additional enrichment analyses may be performed during different and additional periods of time to identify the historical distribution of the variant and/or migration patterns of Variant X. The results of the enrichment analysis and other genealogical data of the cluster are used to characterize the variant associated with the cluster. For example, migration patterns, current and historical distributions, average life span, variant origination, etc. associated with a variant may be identified. The characterization may be presented as a map, as discussed in
In some embodiments, the variant origination engine 235 can assess the analytical validity of a variant from a founder population using IBD as evidence. If a variant is known to have arisen from a founder, the variant origination engine 235 can provide analytical validation of that variant by assessing whether the known carriers of the variant share IBD with each other at the genetic loci around and including the variant. Additionally, the variant origination engine 235 confirms that not all of the known carriers of the variant share IBD collectively with DNA samples that are not ‘positive’ for the variant (e.g., DNA samples of individuals known to not carry the variant).
As the IBD estimation engine 230 identifies additional users that share IBD at the genetic locus of a variant of interest, the variant origination engine 235 provides the characterization of the variant to the additional user. In some embodiments, the variant origination engine 235 adds the additional user to the cluster and reperforms the enrichment analysis using the additional user's DNA sample and genealogical data using various statistical tests (e.g., Fisher's exact test, chi-squared test, and the like). In some embodiments, similar analysis may be performed on phenotypes or haplotypes to characterize a phenotype or haplotype of interest.
The illustration 500 shown depicts the birth locations of individuals who were born between the years 1700 A.D. and 1800 A.D, were carriers of a variant, trait, phenotype, haplotype, etc. of interest, and were born in the United States or Europe. It is shown in
Examples of statistics that are computed during the enrichment analysis include odds ratio and frequency. The odds ratio is defined as the odds that, at a given location, an individual is a carrier of a variant over the odds that the individual is not a carrier of the variant. The log of the odds ratio 510 is used to generate a graph that visually depicts grid points in which the largest log odds ratios are indicated visually by labels or distinguishable shapes. For example, a circle indicates the log of the odds ratio is between 1 and 3; a star indicates the log of the odds ratio is between 3 and 5; a square indicates the log of the odds ratio is between 5 and 7, etc. In this way, the highlighted graphical map locations correspond to birth locations that are disproportionately represented by carriers of the variant of interest. For example, individuals born in Denmark 525 between 1700 A.D. and 1800 A.D. are likely to be carriers of a variant, e.g., Variant X.
The frequency is defined as the fraction of individuals born in a geographic location that carry a variant, trait, haplotype, genotype, etc. of interest (and/or share IBD with individuals that carry the variant of interest) and the total number of individuals born at the geographic location. Frequency can be calculated for distinct time periods to identify the origin, migration patterns, and historical and contemporary distributions of a variant, trait, haplotype, or genotype of interest. The log frequency 515 is used to generate a graph that visually depicts grid points in which the greatest frequency ratios are indicated visually by labels or the size of the marker. The size of the marker indicates a log frequency 515 of the variant in a particular location. As shown, the larger the circle, the more frequently individuals born in a particular location are carriers of the variant. For example, as shown in the illustration 500, on the east coast of the United States 520, individuals born on the East Coast were frequently carriers of Variant X or shared IBD with carriers of Variant X.
In
Individuals are identified as belonging to a community based on the number of enriched haplotypes of a community they have. The more enriched haplotypes of a community they carry, the greater the likelihood they belong to that community. As shown, individuals that have at least a threshold number of enriched haplotypes of Community A are members of Community A. Similarly, individuals that carry less than a threshold number of enriched haplotypes of Community A are not members of Community A. For example, Individual A 615 is a carrier of 12 of the 15 enriched haplotypes of Community A, e.g., haplotype 620 and haplotype 630, and Individual H 625 is only a carrier of 4 of the 15 enriched haplotypes of Community A.
Models are trained using training and testing datasets sets created for each community. Training and testing datasets are generated by phasing the genotypes of individuals who belong to a community of interest and individuals who do not belong to the community of interest. Training of the models may be supervised. For example, each individual in the training and testing datasets may have a binary label indicating whether or not they belong to the community. If an individual is known to belong to a community, the individual is labeled with a “1”. Similarly, if an individual is known to not belong to the community, the individual is labeled with a “0”. Positive training sets comprise groups of haplotypes of individuals known to belong to a community. Negative training sets comprise groups of haplotypes of individuals known to not belong to a community.
The genotypes of the community members are analyzed to find the common haplotypes at each window. For example, common haplotypes are of window lengths of 64, 128, and 512 SNPs). An enrichment analysis is performed on the common haplotypes to find which common haplotypes are more likely to be observed in the community of interest compared to other communities (“enriched haplotypes”) 601. In one embodiment, Fisher's exact tests are used during the enrichment analysis to identify enriched haplotypes. In another embodiment, chi-square tests are used to identify enriched haplotypes. Bonferroni corrections may be used to avoid false positives. Enriched haplotypes, also referred to as reference haplotypes, are used as features in a community-specific model. Models may be linear or non-linear, and may include random forest classifiers, SVMs, neural networks, decision trees. A feature vector is generated for each individual in the training and testing datasets. Each element in the feature vector corresponds to a reference haplotype, and the value of each element indicates the presence or absence of the reference haplotype in the individual. For example, if an individual has a feature, the corresponding element in the feature vector has a value of “1”, and if the individual does not have a feature, the corresponding element in the feature vector has a value of “0”.
The community prediction engine 240 generates a data frame that includes the individuals with their feature vector and the label indicating whether or not they belong in the community. The model is applied to the data frame, and the performance of the model is measured. The analysis of the model may be performed multiple times based on a chosen length of haplotypes (e.g., 64, 128, 512 SNPs). In some embodiments, haplotypes of different lengths are mixed during analysis. In other embodiments, haplotypes of a single length are used during analysis. Final model parameters and weights are chosen based on model performance.
The foregoing description of the embodiments has been presented for the purpose of illustration; it is not intended to be exhaustive or to limit the patent rights to the precise forms disclosed. Persons skilled in the relevant art can appreciate that many modifications and variations are possible in light of the above disclosure.
Some portions of this description describe the embodiments in terms of algorithms and symbolic representations of operations on information. These algorithmic descriptions and representations are commonly used by those skilled in the data processing arts to convey the substance of their work effectively to others skilled in the art. These operations, while described functionally, computationally, or logically, are understood to be implemented by computer programs or equivalent electrical circuits, microcode, or the like. Furthermore, it has also proven convenient at times, to refer to these arrangements of operations as engines, without loss of generality. The described operations and their associated engines may be embodied in software, firmware, hardware, or any combinations thereof.
Any of the steps, operations, or processes described herein may be performed or implemented with one or more hardware or software engines, alone or in combination with other devices. In one embodiment, a software engine is implemented with a computer program product comprising a computer-readable medium containing computer program code, which can be executed by a computer processor for performing any or all of the steps, operations, or processes described.
Embodiments may also relate to an apparatus for performing the operations herein. This apparatus may be specially constructed for the required purposes, and/or it may comprise a general-purpose computing device selectively activated or reconfigured by a computer program stored in the computer. Such a computer program may be stored in a non-transitory, tangible computer readable storage medium, or any type of media suitable for storing electronic instructions, which may be coupled to a computer system bus. Furthermore, any computing systems referred to in the specification may include a single processor or may be architectures employing multiple processor designs for increased computing capability.
Embodiments may also relate to a product that is produced by a computing process described herein. Such a product may comprise information resulting from a computing process, where the information is stored on a non-transitory, tangible computer readable storage medium and may include any embodiment of a computer program product or other data combination described herein.
Finally, the language used in the specification has been principally selected for readability and instructional purposes, and it may not have been selected to delineate or circumscribe the patent rights. It is therefore intended that the scope of the patent rights be limited not by this detailed description, but rather by any claims that issue on an application based hereon. Accordingly, the disclosure of the embodiments is intended to be illustrative, but not limiting, of the scope of the patent rights.
The present application is a continuation of U.S. application Ser. No. 17/531,438, filed on Nov. 19, 2021, which is a divisional application of U.S. application Ser. No. 17/044,223, filed on Apr. 4, 2019, which is a national stage entry of International Application No. PCT/IB2019/052788, filed on Apr. 4, 2019, which claims the benefit of U.S. Provisional Patent Application No. 62/653,416 filed on Apr. 5, 2018, and U.S. Provisional Patent Application No. 62/653,420 filed on Apr. 5, 2018, which are hereby incorporated by reference in their entirety for all purposes.
| Number | Date | Country | |
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| 62653416 | Apr 2018 | US | |
| 62653420 | Apr 2018 | US |
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| Parent | 17044223 | Sep 2020 | US |
| Child | 17531438 | US |
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| Parent | 17531438 | Nov 2021 | US |
| Child | 18642769 | US |
