Biology subjects

Tern, C.

Publications and source records attributed to Tern, C..

3 recordsLinked to original sources

bioRxiv2025

miRNA-mRNA network analysis identifies PAX5 as a potential regulator of adaptive immune response in COPD

Micro-ribonucleic acids (miRNAs) are key post-transcriptional regulators of the immune system and may play a role in Chronic Obstructive Pulmonary Disease (COPD). In this paper, we constructed subject-specific miRNA-mRNA regulatory networks using bulk and deconvoluted whole blood RNA-sequencing, whole blood miRNA-sequencing, and B-cell receptor-sequencing data from up to 570 miRNAs, 11,859 mRNAs, and 3,190 participants in the COPDGene study. Analysis of whole blood networks revealed two subnetworks of miRNA-mRNA interactions significantly (FDR<0.05) associated with changes in FEV1/FVC. We found that miRNAs (and mRNAs) in the network-identified groups had distinct expression patterns, with miRNAs (and mRNAs) in one group having overall higher expression in COPD (decreasing FEV1/FVC) and miRNAs (and mRNAs) in the other group having overall higher expression in controls (increasing FEV1/FVC). In addition, miRNAs (and mRNAs) within the same group were positively correlated, while those in different groups were negatively correlated, indicating distinct functional roles for these miRNAs (and mRNAs) as a function of increased COPD severity. Network analysis also identified PAX5, a transcription factor master regulator of B-cell development, as the main mRNA network hub. Using ChIP-seq data in lymphoblastoid cells, we identified a PAX5 binding site overlapping with a COPD genome-wide association signal in the promoter region of ADAM19. We also found a loss of co-expression between PAX5 and ADAM19 in COPD subjects. Furthermore, in B-cell deconvoluted data, PAX5 was differentially co-expressed with genes associated with B-cell activation and differentiation, revealing a possible mechanism for the regulation of the immune response in COPD. Finally, in B-cell receptor sequencing data, PAX5 and the identified mRNA subnetworks were negatively associated (FDR<0.05) with immunoglobulin class switching, and positively associated with IgM and IgD counts. In conclusion, PAX5 is a known regulator of B-cell identity. B cells are recognized as key players in chronic inflammation and immune dysregulation in COPD. Our work suggests that PAX5 plays a mediating role both in ADAM19 regulation and in miRNA regulation of early B cells in COPD.

systems biology↗

bioRxiv2022

A cosmopolitan inversion drives seasonal adaptation in overwintering Drosophila

Drosophila melanogaster living in temperate regions evolve as they track seasonal fluctuations. Yet, we lack an understanding of the genetic architecture of seasonal adaptive tracking. By sequencing orchard populations collected across multiple years, we characterized the genomic signal of seasonal demography and identified that the cosmopolitan inversion In(2L)t drives seasonal adaptation. In(2L)t shows footprints of selection that are inconsistent with simple explanations of genetic drift, as well as signatures of partial selective sweeps. A meta-analysis of phenotypic studies shows that seasonal loci within In(2L)t are associated with behavior, life-history, physiology, and morphology traits. Our results identify candidate regions that underlie seasonal adaptive tracking and link them to phenotype. This work supports the general hypothesis that inversions are important drivers of rapid adaptation. One-Sentence SummaryA chromosomal inversion drives adaptive evolution between seasons in wild fruit flies.

evolutionary biology↗

bioRxiv2021

Drosophila Evolution over Space and Time (DEST) - A New Population Genomics Resource

Drosophila melanogaster is a leading model in population genetics and genomics, and a growing number of whole-genome datasets from natural populations of this species have been published over the last 20 years. A major challenge is the integration of these disparate datasets, often generated using different sequencing technologies and bioinformatic pipelines, which hampers our ability to address questions about the evolution and population structure of this species. Here we address these issues by developing a bioinformatics pipeline that maps pooled sequencing (Pool-Seq) reads from D. melanogaster to a hologenome consisting of fly and symbiont genomes and estimates allele frequencies using either a heuristic (PoolSNP) or a probabilistic variant caller (SNAPE-pooled). We use this pipeline to generate the largest data repository of genomic data available for D. melanogaster to date, encompassing 271 population samples from over 100 locations in >20 countries on four continents based on a combination of 121 unpublished and 150 previously published genomic datasets. Several of these locations have been sampled at different seasons across multiple years. This dataset, which we call Drosophila Evolution over Space and Time (DEST), is coupled with sampling and environmental meta-data. A web-based genome browser and web portal provide easy access to the SNP dataset. Our aim is to provide this scalable platform as a community resource which can be easily extended via future efforts for an even more extensive cosmopolitan dataset. Our resource will enable population geneticists to analyze spatio-temporal genetic patterns and evolutionary dynamics of D. melanogaster populations in unprecedented detail.

genomics↗