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Biology subjects

Koefoed, T. G.

Publications and source records attributed to Koefoed, T. G..

2 recordsLinked to original sources

multiomeR: a pipeline for reproducible analysis of large-scale single-nucleus Epi Multiome datasets

The 10x Genomics Epi Multiome assay measures gene expression and chromatin accessibility in the same nuclei, and studies increasingly profile many samples. Yet analysis after Cell Ranger ARC is usually assembled by hand from separate tools, which makes it slow to revise, hard to reproduce and memory-intensive for large studies. multiomeR addresses these problems with a configurable R pipeline for quality control, processing and integration of both data types, and cell-type annotation across many samples. Plain-text configuration files record every analytical choice, each step is tracked so that a change reruns only what it affects, and data stay on disk rather than in memory. Optional modules compare groups of donors, link accessible regions to the genes they may regulate, and test which cell types are enriched for genetic associations with a trait. In a benchmark on 31 public samples (375,757 nuclei), multiomeR had a shorter estimated run time than a Seurat v5.6/Signac v2 workflow (2.2 versus 5.6 h), because it runs independent steps in parallel. It also used fewer memory gigabyte-hours (87 versus 114 GB-hours), with similar total CPU time. multiomeR thus makes large multi-sample multiome studies practical to analyze, revise and extend.

bioinformatics↗

Exposure to childhood maltreatment is associated with changes in sperm small non-coding RNA and DNA methylation profiles

BackgroundChildhood maltreatment exposure (CME) increases the risk of adverse long-term health consequences for the exposed individual. Animal studies suggest that CME may also influence the health and behaviour in the next generation offspring through CME-driven epigenetic changes in the paternal germ line. The contribution of paternal early life stress on the health of the next generation in humans is not fully elucidated. MethodsIn this study, we measured paternal CME using the Trauma and Distress Scale (TADS) questionnaire and mapped sperm-borne sncRNAs expression by small RNA sequencing (small RNA-seq) and DNA methylation (DNAme) in spermatozoa by reduced-representation bisulfite sequencing (RRBS-seq) in males from the FinnBrain Birth Cohort Study. The study design was a (nested) case-control study, high-TADS (TADS [≥] 39, n = 25 for DNAme and n = 14 for small RNA-seq) and low-TADS (TADS [≤] 10, n = 30 for DNAme and n = 16 for small RNA-seq)). Groups were compared to identify specific epigenetic signatures associated with TADS levels in the spermatozoa of participants. ResultsCompared to the control group, high CME was associated with altered sperm sncRNA expression and DNAme profiles. Particularly, we identified several tRNA-derived small RNAs (tsRNAs) and miRNAs with markedly changed levels in males with high CME. DNA methylation analysis identified several genomic regions with differentially methylated CpGs between groups. Notably, we identified two epigenetic marks related to brain development with distinct profiles between CME and controls, the miRNA hsa-mir-34c-5p and differential methylation of the region in proximity of FSCN1. ConclusionsThis study provides further evidence that early life stress influences the paternal germ line epigenome and supports a possible contribution in the development of the central nervous system of the next generation.

molecular biology↗