Biology subjects

Hallgrimsdottir, I. B.

Publications and source records attributed to Hallgrimsdottir, I. B..

3 recordsLinked to original sources

bioRxiv2024

Estimating cis and trans contributions todifferences in gene regulation

We describe a coordinate system and associated hypothesis testing framework for determining whether cis or trans regulation is responsible for differences in gene expression between two homozygous strains or species. We apply our framework to data from single replicate studies on yeast strains and human-chimpanzee hybrid cells, as well as to data from a mouse study with replicates, showing marked differences between our gene regulatory assignments and those previously reported. We also show how our multi-sample framework can determine the context dependency of cis and trans effects as well as explicitly model different hypotheses regarding the underlying mechanism of trans regulation.

genetics↗

bioRxiv2023

Direct androgen receptor regulation of sexually dimorphic gene expression in the mammalian kidney

Mammalian organs exhibit distinct physiology, disease susceptibility and injury responses between the sexes. In the mouse kidney, sexually dimorphic gene activity maps predominantly to proximal tubule (PT) segments. Bulk RNA-seq data demonstrated sex differences were established from 4 and 8 weeks after birth under gonadal control. Hormone injection studies and genetic removal of androgen and estrogen receptors demonstrated androgen receptor (AR) mediated regulation of gene activity in PT cells as the regulatory mechanism. Interestingly, caloric restriction feminizes the male kidney. Single-nuclear multiomic analysis identified putative cis-regulatory regions and cooperating factors mediating PT responses to AR activity in the mouse kidney. In the human kidney, a limited set of genes showed conserved sex-linked regulation while analysis of the mouse liver underscored organ-specific differences in the regulation of sexually dimorphic gene expression. These findings raise interesting questions on the evolution, physiological significance, and disease and metabolic linkage, of sexually dimorphic gene activity.

developmental biology↗

bioRxiv2022

Depth normalization for single-cell genomics count data

Genomics data analysis requires normalization of feature counts that stabilizes technical variance, accounts for variable cell sequencing depth, and preserves monotonicity of within-cell feature abundances. We show that normalization via an optimal variance stabilizing transform for negative binomial count data followed by a proportional fitting step (PFlog) is the only feature-relabeling-equivariant method satisfying the three desiderata. We demonstrate superior performance of this method, which is equivalent to a shifted centered-log ratio transform, in comparison to other normalizations on numerous benchmarks across hundreds of single-cell RNA-seq datasets. We further show that both the shifted-log scale and centered-log ratio geometry are important for preserving PCA and k-NN structure.

bioinformatics↗