DOI: 10.5061/dryad.280gb5mpd
title: Integrated trajectories of the maternal metabolome, proteome, and immunome predict labor onset

description: Estimating the time of delivery is of high clinical importance because
 pre- and postterm deviations are associated with complications for the
 mother and her offspring. However, current estimations are inaccurate. As
 pregnancy progresses toward labor, major transitions occur in fetomaternal
 immune, metabolic, and endocrine systems that culminate in birth. The
 comprehensive characterization of maternal biology that precedes labor is
 key to understanding these physiological transitions and identifying
 predictive biomarkers of delivery. Here, a longitudinal study was
 conducted in 63 women who went into labor spontaneously. More than 7000
 plasma analytes and peripheral immune cell responses were analyzed using
 untargeted mass spectrometry, aptamer-based proteomic technology, and
 single-cell mass cytometry in serial blood samples collected during the
 last 100 days of pregnancy. The high-dimensional dataset was integrated
 into a multiomic model that predicted the time to spontaneous labor [R =
 0.85, 95% confidence interval (CI) [0.79 to 0.89], P = 1.2 × 10−40, N =
 53, training set; R = 0.81, 95% CI [0.61 to 0.91], P = 3.9 × 10−7, N = 10,
 independent test set]. Coordinated alterations in maternal metabolome,
 proteome, and immunome marked a molecular shift from pregnancy maintenance
 to prelabor biology 2 to 4 weeks before delivery. A surge in steroid
 hormone metabolites and interleukin-1 receptor type 4 that preceded labor
 coincided with a switch from immune activation to regulation of
 inflammatory responses. Our study lays the groundwork for developing
 blood-based methods for predicting the day of labor, anchored in
 mechanisms shared in preterm and term pregnancies.
description: Blood was collected into EDTA
 tubes, kept on ice, and centrifuged (1500 x g, 20 min) at 4 ̊C within 60
 min. Separated plasma was stored at <sup>–</sup>80°C until
 further processing. The 200μL plasma samples were analyzed by the Genome
 Technology Access Center (St. Louis, MO) using a highly multiplexed,
 aptamer-based platform capturing 1310 proteins (SomaLogic, Inc., Boulder,
 CO). The assay quantifies proteins over a wide dynamic range (&gt; 8
 log) using chemically modified aptamers with slow off-rate kinetics
 (SOMAmer reagents). Each SOMAmer reagent is a unique, high-affinity,
 single-strand DNA endowed with functional groups mimicking amino acid side
 chains. In brief, samples were incubated on 96-well plates with a mixture
 of SOMAmer reagents. Two sequential bead-based immobilization and washing
 steps were used to eliminate nonspecifically-bound proteins, unbound
 proteins, and unbound SOMAmer reagents from protein target-bound reagents.
 After eluting SOMAmer reagents from the target proteins, the
 fluorescently-labeled reagents were quantified on an Agilent hybridization
 array (Agilent Technologies, Santa Clara, CA). Data were normalized in 4
 specific steps and according to assay data quality control procedures
 defined in the good laboratory practice quality system of SomaLogic, Inc.
 Normalization steps control for signal intensity biases introduced by
 differential hybridization efficiencies and the overall brightness of
 plates, collection protocol artifacts, and batch effects between different
 plates.
description: The data files contain the normalized plasma protein data,
 expressed as relative fluorescence units (RFU). Please refer to the ReadMe
 file ('Onset of labor proteomics') for additional
 information.