Biology subjects

Nooranikhojasteh, A.

Publications and source records attributed to Nooranikhojasteh, A..

3 recordsLinked to original sources

bioRxiv2024

Benchmarking Peak Calling Methods for CUT&RUN

Cleavage Under Targets and Release Using Nuclease (CUT&RUN) has rapidly gained prominence as an effective approach for mapping protein-DNA interactions, especially histone modifications, offering substantial improvements over conventional chromatin immunoprecipitation sequencing (ChIP-seq). However, the effectiveness of this technique is contingent upon accurate peak identification, necessitating the use of optimal peak calling methods tailored to the unique characteristics of CUT&RUN data. Here, we benchmark four prominent peak calling tools, MACS2, SEACR, GoPeaks, and LanceOtron, evaluating their performance in identifying peaks from CUT&RUN datasets. Our analysis utilizes in-house data of three histone marks (H3K4me3, H3K27ac, and H3K27me3) from mouse brain tissue, as well as samples from the 4D Nucleome database. We systematically assess these tools based on parameters such as the number of peaks called, peak length distribution, signal enrichment, and reproducibility across biological replicates. Our findings reveal substantial variability in peak calling efficacy, with each method demonstrating distinct strengths in sensitivity, precision, and applicability depending on the histone mark in question. These insights provide a comprehensive evaluation that will assist in selecting the most suitable peak caller for high-confidence identification of regions of interest in CUT&RUN experiments, ultimately enhancing the study of chromatin dynamics and transcriptional regulation.

genomics↗

bioRxiv2024

Archaic Adaptive Introgression in Modern Human Reproductive Genes

Modern humans and archaic hominins, namely Denisovans and Neanderthals, have been demonstrated to have a long history of admixture. Specifically, some of these admixture events have been adaptive and allowed modern humans to adapt to their new environments outside of Africa. Little research has been done on the impact of archaic introgression on genes associated with reproduction. In this study we report evidence of putative adaptive introgression of 118 genes within modern humans that have been previously associated with reproduction in mice or modern humans. From these genes we identified 11 archaic core haplotypes, three that have been positively selected. Additionally, we found that 327 archaic alleles have genome-wide significance for a variety of traits and 308 of these variants were discovered to be eQTLs regulating 176 genes. We highlight that 81% of the archaic eQTLs overlapping a core haplotype region regulate genes expressed in ovaries, prostate, testes, and vagina compared to other tissues. We also found that several of the putatively adaptively introgressed genes in our results are enriched in developmental and cancer pathways. Further, some of these genes have been associated with embryo development and reproductive-inhibiting phenotypes like preeclampsia. Lastly, we found that archaic alleles overlapping an introgressed segment on chromosome 2 are protective against prostate cancer. Taken together, our results describe how archaic haplotypes, when introduced into a modern human background, may be important in regulating development across the lifespan of an individual.

evolutionary biology↗

bioRxiv2024

Exploring adaptive introgression in modern human circadian rhythm genes

Interbreeding between modern humans and archaic hominins, including Neanderthals and Denisovans, occurred as modern humans migrated outside of Africa. Here, we report on evidence of introgression from archaic hominins within genomic regions associated with circadian rhythm and chronotype using 76 worldwide modern human populations from the Human Genome Diversity Project and 1000 Genomes Project. We calculated the extent of regions indicative of adaptive introgression across the autosomes and identified regions that are suggested to be under positive selection. We tested for evidence of a latitudinal cline within 36 core haplotypes along with presenting the likely archaic donor for each of these haplotypes. We identified 265 independent segments that overlap genes described as having a circadian rhythm component or contain variants and segments previously identified as being associated with circadian rhythm or chronotype. Within these segments we found 1,729 archaically derived variants with allele frequencies of at least 40% intersecting 303 genes and intergenic segments. Seventeen of these segments show evidence of positive selection, three of which are found within our core haplotypes. We found that many of our genes are associated with the immune system or gastrointestinal function. Additionally, variants associated with complex traits such as schizophrenia and bipolar disorder are present within our adaptively introgressed regions. Lastly, genes and markers associated with sleep and chronotype phenotypes and serotonin pathways were also found in our adaptive introgression results, potentially signalling selection on genes related to seasonal light variation as modern humans migrated into new environments after leaving Africa. Author summaryAs modern humans migrated out of Africa, they encountered archaic hominins, the Neanderthals and Denisovans, and interbred with them. Signatures of these admixture events can be found in populations across the world. The result of these admixture events has shaped modern human evolution regarding high altitude adaptation, immune function, and skin and hair colour, to name a few. However, much of this information has been gathered with a focus on Eurasian populations using the 1000 Genomes Project samples. Here, we take advantage of newly published resources from 76 worldwide modern human populations to investigate how strongly a role admixture played on modern human circadian rhythm genes. Circadian rhythms have been tied to sleep-wake regulation, immune function, and digestive health. We find evidence for adaptive introgression in over 300 genes and intergenic segments. Many of these genes, like AMIGO2, are associated with complex traits such as schizophrenia and bipolar disorder or with immune system function, like JAK1. Some of these traits have been previously described before regarding archaic admixture. Interestingly, many of these associated traits are influenced by circadian rhythm oscillations, providing a new perspective on interpreting these findings.

genomics↗