Dworak, N. M. | Search bioRxiv

bioRxiv2025

RAWtunda: a Tool to Convert a Multi-Channel Raw Image into TIFF and OME-TIFF Formats

MotivationHigh-resolution biological imaging in spatial biology produces data in many proprietary formats. The lack of compatibility between these formats restricts reproducibility and analysis, creates access issues, and makes early data analysis a challenge. ResultsHere, we introduce a graphical user interface (GUI) application designed to convert proprietary image formats into standardized formats like OME-TIFF and TIFF which we have termed Rawtunda. This tool addresses the need for easy and efficient handling of large, complex imaging data generated in spatial biology and microscopy, facilitating data sharing, analysis, and long-term storage. Featuring an intuitive interface the application supports users in converting.mcd and.ndpi formats, generated from Image Mass Cytometry (IMC) and Digital Pathology scanners, respectively. This resource aims to improve interoperability of spatial biology datasets, streamline data management workflows, and promote reproducibility in imaging research and analysis, preserving crucial image metadata. The app ensures compatibility with downstream tools and is designed for both bioinformaticians and bench biologists without experience in coding. Availability and implementationThe software, the documentation, and examples are available as open-source a https://med.virginia.edu/spatial-biology-core/rawtunda/ under the Copywrite of University of Virginia.

bioinformatics↗

bioRxiv2024

Parp7 generates an ADP-ribosyl degron that controls negative feedback of androgen signaling

AbstractThe androgen receptor (AR) tranduces the effects of circulating and tumor-derived androgens to the nucleus through ligand-induced changes in protein conformation, localization, and engagement with chromatin binding sites. Understanding these events and their integration with signal transduction is critical for defining how AR drives prostate cancer and unveiling pathway features that are amenable to therapeutic intervention. Here, we describe a novel post-transcriptional mechanism that controls AR protein levels on chromatin and associated gene output which is based on a highly selective, inducible degradation mechanism. We find that the mono-ADP-ribosyltransferase PARP7 generates an ADP-ribosyl degron on a single cysteine within the DNA binding domain of AR, which is then recognized by the ADP- ribose reader domain in the ubiquitin E3 ligase DTX2 and degraded by the proteasome. Mathematical modeling of the pathway suggested that PARP7 ADP-ribosylates chromatin-bound AR, a prediction that was validated in cells using an AR mutant that undergoes nuclear import but fails to bind DNA. Lysine- independent, non-conventional ubiquitin conjugation to ADP-ribosyl-cysteine and AR degradation by the proteasome forms the basis of a negative feedback loop that regulates specific modules of AR target genes. Our data expand the repertoire of mono-ADP-ribosyltransferase enzymes to include gene regulation based on highly selective protein degradation. One Sentence SummaryPARP7 mono-ADP-ribosylates the androgen receptor on Cys620 to mark the androgen receptor for ubiquitin conjugation by an E3 ligase with ADP-ribose reader function, resulting in in negative feedback of AR-dependent gene expression.

cancer biology↗