Multiomics modeling of the immunome, transcriptome, microbiome, proteome and metabolome adaptations during human pregnancy

Mohammad Sajjad Ghaemi(Transport Canada), Daniel B. DiGiulio(VA Palo Alto Health Care System), Kévin Contrepois(Stanford University), Benjamin J. Callahan(North Carolina State University), Thuy T. M. Ngo(Oregon Health & Science University), Brittany Lee‐McMullen(Stanford University), Benoit Lehallier(Stanford University), Anna Robaczewska(VA Palo Alto Health Care System), David R. McIlwain(Stanford University), Yael Rosenberg‐Hasson, Ronald J. Wong(Stanford University), Cecele C. Quaintance(Stanford University), Anthony Culos(Stanford University), Natalie Stanley(Stanford University), Athena Tanada(Stanford University), Amy S. Tsai(Stanford University), Dyani Gaudillière(Stanford University), Edward A. Ganio(Stanford University), Xiaoyuan Han(Stanford University), Kazuo Ando(Stanford University), Leslie McNeil(Stanford University), Martha Tingle(Stanford University), Paul H. Wise(Stanford University), Ivana Marić(Stanford University), Marina Sirota(University of California, San Francisco), Tony Wyss‐Coray(Stanford University), Virginia D. Winn(Stanford University), Maurice L. Druzin(Stanford University), Ronald S. Gibbs(Stanford University), Gary L. Darmstadt(Stanford University), David B. Lewis(Stanford University), Vahid Partovi Nia(Group for Research in Decision Analysis), Bruno Agard(Transport Canada), Robert Tibshirani(Stanford University), Garry P. Nolan(Stanford University), M Snyder(Stanford University), David A. Relman(VA Palo Alto Health Care System), Stephen R. Quake(Stanford University), Gary M. Shaw(Stanford University), David K. Stevenson(Stanford University), Martin S. Angst(Stanford University), Brice Gaudillière(Stanford University), Nima Aghaeepour(Stanford University)
Bioinformatics
June 28, 2018
10.1093/bioinformatics/bty537
Cited by 196Open Access
Full Text

Abstract

Motivation: Multiple biological clocks govern a healthy pregnancy. These biological mechanisms produce immunologic, metabolomic, proteomic, genomic and microbiomic adaptations during the course of pregnancy. Modeling the chronology of these adaptations during full-term pregnancy provides the frameworks for future studies examining deviations implicated in pregnancy-related pathologies including preterm birth and preeclampsia. Results: We performed a multiomics analysis of 51 samples from 17 pregnant women, delivering at term. The datasets included measurements from the immunome, transcriptome, microbiome, proteome and metabolome of samples obtained simultaneously from the same patients. Multivariate predictive modeling using the Elastic Net (EN) algorithm was used to measure the ability of each dataset to predict gestational age. Using stacked generalization, these datasets were combined into a single model. This model not only significantly increased predictive power by combining all datasets, but also revealed novel interactions between different biological modalities. Future work includes expansion of the cohort to preterm-enriched populations and in vivo analysis of immune-modulating interventions based on the mechanisms identified. Availability and implementation: Datasets and scripts for reproduction of results are available through: https://nalab.stanford.edu/multiomics-pregnancy/. Supplementary information: Supplementary data are available at Bioinformatics online.

Related Papers

Classification and Regression by randomForest
Andy Liaw, Matthew C. Wiener|Unknown|2007|18.4k
Stacked generalization
David H. Wolpert|Neural Networks|1992|7.4k
Temporal and spatial variation of the human microbiota during pregnancy
Daniel B. DiGiulio, Benjamin J. Callahan, Paul J. McMurdie et al.|Proceedings of the National Academy of Sciences|2015|1.2k
Prolactin induces phosphorylation of Tyr694 of Stat5 (MGF), a prerequisite for DNA binding and induction of transcription.
Fabrice Gouilleux, Hiroshi Wakao, Maren Mundt et al.|The EMBO Journal|1994|598
A Review of Ensemble Methods in Bioinformatics
Pengyi Yang, Yee Hwa Yang, Bing Bing Zhou et al.|Current Bioinformatics|2010|515