Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.03.30.715300

An atlas of transcriptional dynamics in maternal blood over the course of healthy pregnancy

Feenstra, B.·Hede, F. R. D.·Piening, B. D.·Skotte, L.·Nastou, K.·Liang, L.·Fadista, J.·Rasmussen, M.-L. H.·Scheller, N. M.·Jiang, C.·Vallania, F.·Wei, E.·Liu, Q.·Chaib, H.·Geller, F.·Boyd, H. A.·Snyder, M. P.·Melbye, M.
View original source ↗Export metadata ↓

Abstract

Pregnancy results in profound physiological changes driven by dynamic and precisely programmed molecular processes. Maternal peripheral blood is generally the specimen of choice for studying these processes, as it is easily accessible and essential for many aspects of maintaining a healthy pregnancy. Here, we present a high-resolution atlas of the dynamic temporal changes in the transcriptome of maternal peripheral blood in healthy human pregnancy. We generated comprehensive RNA sequencing data in 802 weekly samples from 31 healthy pregnant women from the first trimester until after delivery. Using a strict discovery and replication setup, our longitudinal analysis of gene expression identified 720 genes with robust pregnancy-specific expression patterns. Using weighted graph correlation network analysis, we identified nine pregnancy-associated transcriptional modules that reveal a strong, coordinated enrichment of innate/neutrophil and antiviral immune programs, alongside changes in adaptive immunity (T cell differentiation and signaling), erythropoiesis and hemoglobin metabolism. Cell-type deconvolution revealed that these transcriptomic shifts were accompanied by increased relative neutrophil proportions and reduced naive CD4 and CD8 T cells in pregnancy. We provide a comprehensive characterization of dynamic changes across pregnancy, highlighting maternal blood as a key systemic regulator in healthy gestation. Together, our findings establish a reference atlas of healthy pregnancy, which can be used to identify dysregulated processes and mechanisms in women with pregnancy complications. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=168 SRC="FIGDIR/small/715300v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@e6dd97org.highwire.dtl.DTLVardef@de217dorg.highwire.dtl.DTLVardef@168ad94org.highwire.dtl.DTLVardef@15c0dd1_HPS_FORMAT_FIGEXP M_FIG C_FIG O_LI720 genes showed robust pregnancy specific expression patterns. C_LIO_LICo-expression analysis clustered the genes into nine modules with distinct dynamics. C_LIO_LIEnrichment in pathways involved in innate and neutrophil-mediated immunity, antiviral responses, T cell differentiation and signaling, erythropoiesis and hemoglobin metabolism. C_LIO_LICell-type deconvolution showed increases in neutrophils and decreases in naive CD4 and CD8 T cells. C_LIO_LIThe atlas of detailed longitudinal transcriptional changes provides a baseline reference for healthy pregnancy. C_LIO_LIResults for all genes and protein-protein interaction networks are made available for interactive exploration. C_LI

Explore related subjects

genomicsPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Feenstra, B., Hede, F. R. D., Piening, B. D., Skotte, L., Nastou, K., Liang, L., Fadista, J., Rasmussen, M.-L. H., Scheller, N. M., Jiang, C., Vallania, F., Wei, E., Liu, Q., Chaib, H., Geller, F., Boyd, H. A., Snyder, M. P., Melbye, M.. 2026-04-01. An atlas of transcriptional dynamics in maternal blood over the course of healthy pregnancy. https://doi.org/10.64898/2026.03.30.715300

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

PfPHAST: Plasmodium falciparum Public Health Amplicon Sequencing Tool, a Streamlined Panel for Malaria Genomic Surveillance

Genomic tools can support malaria control policy through surveillance of Plasmodium falciparum populations, tracking antimalarial drug resistance, pfhrp2/3 deletions that compromise rapid diagnostic tests, and selection at the circumsporozoite protein (PfCSP) vaccine target, as well as through molecular correction of therapeutic efficacy studies (TES). Multiplex Amplicons for Drug, Diagnostic, Diversity, and Differentiation Haplotypes using Targeted Resequencing (MAD4HatTeR), a comprehensive amplicon sequencing panel covering up to 276 targets, supports these applications but is tailored to research rather than routine programmatic use. We developed P. falciparum Public Health Amplicon Sequencing Tool (PfPHAST), a 56-target derivative of MAD4HatTeR spanning drug resistance loci, pfhrp2/3 deletion, PfCSP genotyping, non-falciparum species identification, and 20 high-heterozygosity microhaplotype loci for TES classification. We compared PfPHAST and MAD4HatTeR using laboratory strain controls, including two-strain dilution series and a five-strain mixture, across parasite densities of 100 to 10,000 parasites/L. At matched per-target depth, PfPHAST achieved a higher quality-control pass rate than MAD4HatTeR (94.4% versus 90.0%) and distributed reads more evenly across targets. The panels showed comparable recall and precision for drug resistance codons and microhaplotypes, reaching near-complete recall above 40% within-sample allele frequency (WSAF) at all densities, with reduced sensitivity for minor alleles below 10% WSAF at low parasite density in both panels. Observed and expected WSAF correlated strongly for both panels, and both resolved a five-strain polyclonal mixture, including a 5% minor strain. By concentrating sequencing capacity on targets of greatest programmatic relevance, PfPHAST offers a scalable, lower-cost alternative to comprehensive research panels without sacrificing performance on shared targets, complementing MAD4HatTeR for routine molecular malaria surveillance.

genomics↗
bioRxiv2026

Structural variation in repeat elements is widespread in normal human tissues and in tumorigenesis

Somatic mosaicism contributes to genomic variation, yet postzygotic structural variants remain under-characterized. We performed long- and short-read WGS from multiple individuals (n=47 normal tissues; n=168 samples) and identified mosaic structural variants in all individuals and germ layers, impacting a median 285.2 kb/genome. Nearly half of breakpoints were independently validated, with tissue distributions reflecting both early and late developmental origins. Most mosaic variants were repeat-mediated and 8.3% overlapped functional elements, an enrichment compared to germline variants. To extend these analyses in samples where long-read sequencing is infeasible, we measured repeat alterations from short-read sequencing, recapitulating mosaic tissue-specific differences. We characterized tumor- and tissue- specific variation in repeats across 15 cancer types and found tumor-related repeat variation to be similar in scale to that of normal mosaic variation. Tracking repeat changes in cell-free DNA provided a noninvasive approach for tumor monitoring. Our analyses revealed widespread repeat-driven structural variation in health and disease.

genomics↗
bioRxiv2026

RNA isoform-resolved multiplexed sequencing with bioorthogonal barcoding

RNA isoform dysregulation drives disease pathogenesis and is the target of FDA-approved splice-switching therapeutics. However, multiplexed sequencing methods discard splice junction information because only 3' termini are barcoded and counted. Here, we repurpose acylation and click chemistries to conjugate bioorthogonal barcodes (bobcodes) directly onto multiple internal positions along cellular RNAs. Bobcoded RNAs from multiple samples are pooled for multiplexed cDNA synthesis, during which reverse transcriptase switches from each RNA template onto its tethered bobcode with greater than 99% accuracy in species mixing experiments. Bobcode attachment intervals set cDNA insert sizes without a library fragmentation step, and priming with poly(dT) or random hexamers selects between 3'-end counting and full-length isoform capture. A bioorthogonal barcode-sequencing (BOB-seq v0.1) drug screen identifies transcriptome-wide on- and off-target RNA splicing effects and outperforms existing multiplexing RNA sequencing methods in workflow simplicity, sample-to-sample variability, and barcoding accuracy. Bobcodes add isoform resolution to scalable multiplexed RNA sequencing.

genomics↗