Multiomics Modeling of the Immunome, Transcriptome, Microbiome, Proteome, and Metabolome Adaptations During Pregnancy. 

Mohammad Sajjad Ghaemi, Daniel B. DiGiulio, Kévin Contrepois, Benjamin Callahan, Thuy T. M. Ngo, Brittany Lee-McMullen, Benoit Lehallier, Anna Robaczewska, David Mcilwain, Yael Rosenberg-Hasson, Ronald J Wong, Cecele Quaintance, Anthony Culos, Athena Tanada, Amy Tsai, Dyani Gaudilliere, Edward Ganio, Xiaoyuan Han, Kazuo Ando, Leslie McNeil, Martha Tingle, Paul Wise, Ivana Maric, Marina Sirota, Tony Wyss-Coray, Virginia D Winn, Maurice L. Druzin, Ronald Gibbs, Gary L Darmstadt, David B Lewis, Vahid Partovi Nia, Bruno Agard, Robert Tibshirani, Garry Nolan, Michael P. Snyder, David A. Relman, Stephen R. Quake, Gary M. Shaw, David K. Stevenson, Martin S. Angst, Brice Gaudilliere, Nima Aghaeepour. Bioinformatics, 2018.

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: Materials for reproduction of the results are available here.