Biology subjects

Mualim, K.

Publications and source records attributed to Mualim, K..

2 recordsLinked to original sources

bioRxiv2025

marApp: An R package and web portal to calculate mutations- and genetic diversity-area relationship for conservation

International conservation policies including the Kunming-Montreal Global Biodiversity Framework now consider genetic diversity of wild species in their targets. However, scalable, theory-driven tools to assess and predict genetic diversity loss are still emerging, limiting their use in conservation planning. Analogous to the species-area relationship, recent work has shown that genetic diversity scales with area, described by the mutations-area relationship (MAR) or genetic-diversity-area relationship (GDAR), can approximate the genetic diversity loss in a species from habitat reduction. To enable application of these insights for conservation practitioners and policy makers, we present the mar R package and marApp web portal, a fast and user-friendly tool for MAR/GDAR analysis. The mar package connects genetic diversity patterns in space to ecological theory, and automates steps from reading genetic and geographic data to simulating various habitat extinction scenarios using MAR/GDAR. The mar package estimates only short-term genetic diversity, providing a lower-limit for the far greater long-term genetic losses, underscoring the need to maximize present-day habitat conservation before it becomes irreversible. As a case example, we showcase predictions of coral (Acropora sp.) genetic diversity loss from reef coverage impacts. We demonstrate the usage of marApp without requirements for prior genetics or coding experiences, and provide downloadable reports for conservation.

ecology↗

bioRxiv2020

Genome-wide maps of enhancer regulation connect risk variants to disease genes

Genome-wide association studies have now identified tens of thousands of noncoding loci associated with human diseases and complex traits, each of which could reveal insights into biological mechanisms of disease. Many of the underlying causal variants are thought to affect enhancers, but we have lacked genome-wide maps of enhancer-gene regulation to interpret such variants. We previously developed the Activity-by-Contact (ABC) Model to predict enhancer-gene connections and demonstrated that it can accurately predict the results of CRISPR perturbations across several cell types. Here, we apply this ABC Model to create enhancer-gene maps in 131 cell types and tissues, and use these maps to interpret the functions of fine-mapped GWAS variants. For inflammatory bowel disease (IBD), causal variants are >20-fold enriched in enhancers in particular cell types, and ABC outperforms other regulatory methods at connecting noncoding variants to target genes. Across 72 diseases and complex traits, ABC links 5,036 GWAS signals to 2,249 unique genes, including a class of 577 genes that appear to influence multiple phenotypes via variants in enhancers that act in different cell types. Guided by these variant-to-function maps, we show that an enhancer containing an IBD risk variant regulates the expression of PPIF to tune mitochondrial membrane potential. Together, our study reveals insights into principles of genome regulation, illuminates mechanisms that influence IBD, and demonstrates a generalizable strategy to connect common disease risk variants to their molecular and cellular functions.

genetics↗