Benchmarking sequencing methods and tools that facilitate the study of alternative polyadenylation.

Background: Alternative cleavage and polyadenylation (APA), an RNA processing event, occurs in over 70% of human protein-coding genes. APA results in mRNA transcripts with distinct 3' ends. Most APA occurs within 3' UTRs, which harbor regulatory elements that can impact mRNA stability, translation, and localization.

Divergence in alternative polyadenylation contributes to gene regulatory differences between humans and chimpanzees.

While comparative functional genomic studies have shown that inter-species differences in gene expression can be explained by corresponding inter-species differences in genetic and epigenetic regulatory mechanisms, co-transcriptional mechanisms, such as alternative polyadenylation (APA), have received little attention. We characterized APA in lymphoblastoid cell lines from six humans and six chimpanzees by identifying and estimating the usage for 44,432 polyadenylation sites (PAS) in 9518 genes. Although APA is largely conserved, 1705 genes showed significantly different PAS usage (FDR 0.

Diminished cytokine-induced Jak/STAT signaling is associated with rheumatoid arthritis and disease activity.

Rheumatoid arthritis (RA) is a systemic and incurable autoimmune disease characterized by chronic inflammation in synovial lining of joints. To identify the signaling pathways involved in RA, its disease activity, and treatment response, we adapted a systems immunology approach to simultaneously quantify 42 signaling nodes in 21 immune cell subsets (e.g.

Negotiated Sharing of Pandemic Data, Models, and Resources.

Urgent responses to the COVID-19 pandemic depend on increased collaboration and sharing of data, models, and resources among scientists and researchers. In many scientific fields and disciplines, institutional norms treat data, models, and resources as proprietary, emphasizing competition among scientists and researchers locally and internationally. Concurrently, long-standing norms of open data and collaboration exist in some scientific fields and have accelerated within the last two decades.

Alternative polyadenylation mediates genetic regulation of gene expression.

Little is known about co-transcriptional or post-transcriptional regulatory mechanisms linking noncoding variation to variation in organismal traits. To begin addressing this gap, we used 3' Seq to study the impact of genetic variation on alternative polyadenylation (APA) in the nuclear and total mRNA fractions of 52 HapMap Yoruba human lymphoblastoid cell lines. We mapped 602 APA quantitative trait loci (apaQTLs) at 10% FDR, of which 152 were nuclear specific.