COMPOSITIONS AND METHODS OF PREDICTING TIME TO ONSET OF LABOR

Abstract

Multiparametric analysis is performed at the single cell level of biological samples obtained from an individual during pregnancy to obtain a determination of changes in the interactome, integrating metabolome, immunome and proteome features during pregnancy that are predictive of time to onset of labor.

Description

Claims

1. A method for assessing time to onset of labor for an individual during pregnancy, the method comprising: obtaining at two or more time-points during pregnancy a blood-based sample from the individual, comprising one or more features selected from: plasma proteins, metabolites and immune cells;quantitating one or more of the features at the two or more time points;determining whether changes in the features associated with onset of labor are present; andproviding an assessment of the individual’s time to onset of labor.

2. The method of claim 1, wherein treatment of the individual is made in accordance with the assessment.

3. The method of claim 1, wherein the two or more time-points are within second or third trimester of the pregnancy.

4. The method of claim 1, wherein the two or more timepoints are within the third trimester of the pregnancy.

5. The method of claim 1, wherein a sample is obtained at least 3, 4, 5, 6, 7, 8, 9, 10 time points.

6. The method of claim 1, wherein the trajectory of changes in a feature is determined.

7. The method of claim 1, wherein the quantitated features are selected from: 331.2264_8.4 (17-OHP/P4 derivative); 331.2264_8.1 (17-OHP/P4 derivative); 331.2265_8.9 (17-OHP/P4 derivative); 361.2017_7.1 (Cortisol); 415.3204_12 (C27H42O3); 151.0615_2.6 (1-Methylhypoxanthine); 411.1844_8.7 (17-OH pregnenolone sulfate); 193.0618_5.3 (4-Aminohippuric acid); 151.0612_6 (Arabitol, Xylitol); 219.0774_6.3 (5-Hydroxytryptophan); 236.0929_4.3 (N-Lactoylphenylalanine); 397.205_10.6 (6 (Pregnanolone sulfate); IL-1R4; Plexin-B2 (PLXB2); Discoidin domain receptor 1 (DDR1); Angiopoietin-2; Vascular Endothelial Growth Factor 121; Cystatin C; SLIT and NTRK-like protein 5 (SLTRK5); Secr. Leukocyte Peptidase Inhibitor (SLPI); Activin A; Antithrombin III; Macrophage inhibitory cytokine-1 (MIC-1); Siglec-6; urokinase-type Plasminogen Activator (uPA); Matrix Metalloproteinase (MMP) 12; Soluble tunica interna endothelial cell kinase (sTie)-2; LAG3; Endostatin; GA733-1 protein; CD69-CD56loCD16+NK, pSTAT1, IFNα; Granulocytes (freq); CD69+CD56loCD16+NK, pSTAT1, IFNα; CD62L+CD4Tnaive, pMAPKAPK2, IFNα; ncMC, pCREB, GM-CSF; CD69+CD8Tmem, pMAPKAPK2, basal; pDC, pSTAT1, IFNα; B cells, pMAPKAPK2, LPS; CD4Tem, pMAPKAPK2, basal; CD69+CD8Tmem, pMAPKAPK2, IFNα; B cells (freq); CCR5+CCR+CD4Tem, pNFκB, IL-2,4,6; CCR+CCR2+CD4Tcm, IκB, basal; DC, pSTAT6, IFNα; DC, pMAPKAPK2, basal.

8. The method of claim 1, wherein the quantitated features comprise IL-1 receptor type 4 (IL-1R4); Activin-A; Sialic Acid Binding Ig Like Lectin (Siglec)-6; antithrombin III (ATIII); soluble tunica interna endothelial cell kinase (sTie)-2; PLXB2; DDR1; Angiopoietin-2; and vascular endothelial growth factor (VEGF)121.

9. The method of claim 1, wherein the quantitated features comprise: cortisol, Angiopoietin-2; granulocytes (frequency); isomers of 17-hydroxyprogesterone (17-OHP); 17-hydroxypregnenolone sulfate; IL-1 receptor type 4 (IL-1R4); dendritic cells pSTAT6 response to interferon α; soluble tunica interna endothelial cell kinase (sTie)-2; and CD69-CD56loCD16+NK cell pSTAT1 response to IFNα.

10. The method of claim 1, wherein the quantitated features comprise: phosphorylated (p)STAT1 signal in CD56dimCD16+ NK cells and the pSTAT6 signal in dendritic cells (DCs) in response to IFNα, the pP38, pERK and pCREB signals in classical monocytes (cMCs) in response to LPS and GM-CSF, and the pCREB response in non-classical monocytes (ncMCs) in response to GM-CSF.

11. The method of claim 1, wherein from 5 to 15 features are quantitated.

12. The method of claim 1, wherein from 5 to 10 features are quantitated.

13. The method of claim 1, wherein the quantitated features comprise: isomers of 17-hydroxyprogesterone (17-OHP); and 17-hydroxypregnenolone sulfate.

14. The method of claim 1, wherein the quantitated features comprise features from metabolome, proteome and immunome.

15. The method of claim 1, wherein multiple features are integrated in a multivariate model.

16. The method of claim 15, wherein a stacked generalization (SG) algorithm is applied to a dataset of feature quantitation measurements for an integrated model, where linear regression models a first individually built for each feature dataset, then integrated into a single model by SG.

17. The method of claim 1, wherein immunome features are quantitated by flow cytometry.

18. The method of claim 1, wherein metabolome features are assessed by mass spectroscopy.

19. The method of claim 1, wherein proteome features are assessed by affinity binding.