Biology subjects

melnick, m.

Publications and source records attributed to melnick, m..

2 recordsLinked to original sources

bioRxiv2026

Dogcatcher2: Improved statistical detection of transcriptional readthrough and repetitive element analysis across sequencing platforms

Downstream of Gene (DoG) transcription occurs when RNA polymerase II fails to terminate normally at the transcription end site, resulting in extended transcription downstream of the gene. This is a widespread phenomenon linked to cellular stress, cancer and neurodegeneration. Existing tools for DoG detection from short-read RNA-seq rely on absolute coverage thresholds and sliding window approaches that are sensitive to sequencing depth and expression level. Here we present Dogcatcher2, which applies improved statistical detection methods to gene body-normalized coverage profiles. Using long-read ground truth across multiple datasets, we show that Dogcatcher2 outperforms existing methods in both detection sensitivity and boundary accuracy while maintaining high precision even at low sequencing depths. Dogcatcher2 further improves detection on pseudobulk scRNA-seq and snRNA-seq data. Analysis of DoG regions in human reveals specific enrichment for Alu elements including inverted Alu pairs capable of forming double-stranded RNA, with transposable elements within DoG regions showing elevated expression, connecting readthrough transcription to dsRNA generation and innate immune signaling.

bioinformatics↗

bioRxiv2018

Heat Shock in C. elegans Induces Downstream of Gene Transcription and Accumulation of Double-Stranded RNA

We observed that heat shock of Caenorhabditis elegans leads to the formation of nuclear double-stranded RNA (dsRNA) foci, detectable with a dsRNA-specific monoclonal antibody. These foci significantly overlap with nuclear HSF-1 granules. To investigate the molecular mechanism(s) underlying dsRNA foci formation, we used RNA-seq to globally characterize total RNA and immunoprecipitated dsRNA from control and heat shocked worms. We find antisense transcripts are generally increased after heat shock, and a subset of both sense and antisense transcripts enriched in the dsRNA pool by heat shock overlap with dsRNA transcripts enriched by deletion of tdp-1, which encodes the C. elegans ortholog of TDP-43. Interestingly, transcripts involved in translation are over-represented in the dsRNAs induced by either heat shock or deletion of tdp-1. Also enriched in the dsRNA transcripts are sequences downstream of annotated genes (DoGs), which we globally quantified with a new algorithm. To validate these observations, we used fluorescence in situ hybridization (FISH) to confirm both antisense and downstream of gene transcription for eif-3.B, one of the affected loci we identified.

molecular biology↗