Biology subjects

Starkenburg, S. R.

Publications and source records attributed to Starkenburg, S. R..

4 recordsLinked to original sources

bioRxiv2024

Epigenomic manipulation reveals the relationship between locus specific chromatin dynamics and gene expression

Dysregulation of epigenetic processes leads to a plethora of abnormalities including disease states such as cancer. Therapies focused on epigenetic modulation alter gene expression to correct dysfunction, though the mechanisms and perpetuation of these states is unknown. Here, we use integrated epigenomics and three-dimensional chromatin structure-function analyses after acute histone deacetylase inhibitor cancer drug treatment (suberoylanilide hydroxamic acid in lung cancer cells). Treatment induced substantial (13%) genomic rearrangement that rebounds despite persistent gene expression changes and spreading of acetylation. The chromatin functional landscape (accessibility, active transcription modification, and gene expression) is controlled and locus-specific, while chromatin contacts are globally altered resulting in a moderate weakening of topologically associating domains. Chromatin states are more dynamic at transcriptionally active loci while genes with reduced expression are epigenetically stable suggesting chromatin architectural turnover and nucleosome remodeling is locus-specific and underlies the bidirectional expression changes. Thus, local 3D chromatin and genome structural dynamics is integral for loci regulation in response to epigenomic perturbation. The partial persistence of these altered features may have larger implications for efficacy of epigenetic drugs in amelioration of disease states.

cancer biology↗

bioRxiv2024

SLUR(M)-py: A SLURM Powered Pythonic Pipeline for Parallel Processing of 3D (Epi)genomic Profiles

Epigenomics has become multi-faceted, with researchers exploring chromatin structure, nucleosome states, and epigenetic modifications, producing large, complex multi-omic data sets. Given this shift, there is de-mand for bioinformatics that leverage high performance computing (HPC) and parallelization to quickly process data. As such, we developed SLUR(M)-py: a pythonic computational platform that leverages the Simple Linux Utility for Resource Management system (SLURM) to process sequencing data. SLUR(M)-py is multi-omic and automates calls to SLURM for processing paired-end sequences from chromatin charac-terization experiments, including whole-genome, ChIP-seq, ATAC-seq, and Hi-C, thereby eliminating the need for multiple analytics pipelines. To demonstrate SLUR(M)-pys utility, we employ ATAC-seq and Hi-C data from viral infection experiments and the ENCODE project, and illustrate its processing speed and completeness, which outpaces current HPC pipelines. We explore the effect of dropping duplicate se-quenced reads in ATAC-seq, demonstrate how SLUR(M)-py can be used for quality control, and how to detect artifacts in Hi-C from viral infection experiments. Finally, we show how features in SLUR(M)-py, like inter-chromosomal analysis, can be used to explore the dynamics of chromosomal contacts in mammalian cells. This multi-omic, system agnostic platform eases the computational burden for researchers and quickly produces accurate, reliable data analytics for the epigenomics community.

bioinformatics↗

bioRxiv2023

Vaccinia virus infection induces concurrent alterations in host chromatin architecture, accessibility, and gene expression

Genomic DNA folds into complex configurations that produce particular local and global structures thought to profoundly impact genome function. To understand the dynamic nature of this relationship, we investigated the extent of host chromatin structural and functional changes in response to a viral agent. We performed comprehensive assessments of host architecture (Hi-C), accessibility (ATAC-seq), and gene expression (RNA-seq) in a paired manner in response to attenuated vaccinia (smallpox) virus. Over time, infection significantly increased long-range intra-chromosomal interactions and decreased chromatin accessibility. Fine-scale accessibility changes were independent of broad-scale chromatin compartment exchange, which increased (up to 12% of the genome) over time, underscoring potential independent mechanisms for global and local chromatin reorganization. The majority of differentially expressed genes, including those downregulated in immune responses, had concurrent alterations in local accessibility and loop domain restructuring. Increased B compartmentalization, intra-chromosomal interactions, and decreased inter-chromosomal interactions and chromatin accessibility together indicate that infection converts the host genome into a more condensed state with nearly equal bidirectional differential gene expression. These changes in host chromatin features may have implications for developing efficacious anti-viral countermeasures. Overall, our empirical data provides evidence of orchestrated concurrent alterations in chromatin architecture, accessibility, and gene expression in response to infection, further reinforcing the notion of coordinated structure-function dynamics of the genome.

genomics↗

bioRxiv2022

The telomere-to-telomere, gapless, phased diploid genome and methylome of the green alga Scenedesmus obliquus UTEX 3031 reveals significant heterozygosity and functional separation of the haplotypes

Recent advances in sequencing technologies have improved contiguity of de novo genome assemblies. Nevertheless, the genomes of all eukaryotic organisms which are polyploid remain unfinished, limiting understanding of genetic and structural variation in diploid or polyploid organisms. Herein, we report the methodology and analysis of a 100% complete, gapless, phased, telomere-to-telomere diploid genome assembly of the eukaryote, Scenedesmus obliquus UTEX 3031 (DOE0152Z). Analysis of the fully assembled and resolved haplotypes revealed significant genomic rearrangements. Inter-haplotype heterogeneity was significant on most chromosomes yet one chromosome pair (Chromosome 15) was found to contain nearly no heterozygosity. Analysis of the 5mC methylation patterns revealed divergence in active gene content across haplotypes. Assembly of fully resolved chromosome pairs enabled complete resolution of genomic rearrangements and heterogeneity of haplotypes, the genomic basis of trait gain/loss, and evolutionary divergence across chromosome pairs. Further, when combined with 5mC methylation patterns, the assembly provides critical annotation information for genetic engineering approaches to achieve full knock-outs in allelic pairs.

genomics↗