Biology subjects

Munoz-Esquivel, G.

Publications and source records attributed to Munoz-Esquivel, G..

4 recordsLinked to original sources

bioRxiv2026

fastCDS: proteome-scale mapping of protein domains to genomic coordinates

SummaryMapping protein regions to genomic coordinates underpins the study of exon architecture and the interpretation of clinical variants in their exon context. Existing tools resolve individual queries accurately but scale poorly to proteome-wide analyses. We present fastCDS, a C++ toolkit with command line and Python interfaces for rapid protein-to-genome coordinate mapping from GTF annotations. It matches the accuracy of existing methods while running at least two to three orders of magnitude faster. Mapping all human Pfam domains in seconds, we used the resulting atlas to examine how exonic architecture varies with domain function. Availability and ImplementationfastCDS is freely available under the MIT license at {{https://github.com/SotoLF/fastCDS}} and can be installed with pip install fastCDS or mamba install -c bioconda fastCDS. Pre-built GTF genome indices are archived at Zenodo, DOI: https://zenodo.org/records/21436146. Contactlsoto@rockefeller.edu Supplementary InformationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2026

Atlas of HIV cis-regulatory elements reveals extensive transcriptional variation across clades, isolates, and within individuals

Human immunodeficiency virus (HIV) replication, persistence, and reactivation depend on transcription from integrated proviruses. Despite extensive sequence variation, how viral genetic diversity influences transcriptional regulation remains poorly understood. Here, we generate a functional regulatory atlas of HIV-1 and HIV-2 by combining tiling and saturation mutagenesis massively parallel reporter assays (MPRAs) with comparative sequence analysis and predictive modeling. By profiling thousands of HIV isolates in Jurkat and human primary CD4+T cells, we reveal extensive variation in baseline and stimulus-induced long terminal repeat (LTR) activity across and within clades, driven by distinct transcription factor configurations. These activities frequently differ among proviruses from the same individual and shift over infection and transmission without consistent selection for activity. Beyond the LTR, we identify conserved intragenic cis-regulatory elements, revealing regulatory architectures that complement LTR activity. Finally, we develop sequence-based models that accurately predict transcriptional activity, enabling scalable functional annotation of viral diversity and evolution.

microbiology↗

bioRxiv2025

Viral transcriptional regulators extensively rewire host pathways through diverse mechanisms

Viral transcriptional regulators (vTRs) reprogram host gene regulatory networks to promote replication, persistence, and immune evasion. Despite the identification of hundreds of vTRs in human viruses, how they rewire host pathways remains unclear. Here, we systematically profiled 95 vTRs from diverse human viruses across multiple functional assays. vTRs perturb immune, cell proliferation/death, and signaling pathways through various mechanisms; some bind DNA directly, others cooperate or antagonize human transcription factors (hTFs), and some remodel chromatin. vTRs can act as activators or repressors and recruit similar but not identical repertoires of proteins as hTFs. These findings reveal vTRs as versatile transcriptional modulators that converge on conserved host "pressure points" while diversifying across pathways to promote viral replication and persistence. Notably, many vTR dysregulate genes within autoimmune, neurological, and cardiovascular risk loci, revealing mechanistic links to disease. Together, we provide a comprehensive resource for understanding and targeting viral control of human transcription.

genomics↗

bioRxiv2025

Global cis-regulatory landscape of double-stranded DNA viruses

Most double-stranded DNA (dsDNA) viruses use the host transcriptional machinery to express viral genes for replication and immune evasion. This is mediated by viral cis-regulatory elements (CREs) regulated by host and viral transcription factors (TFs). Although some viral CREs and their regulatory mechanisms have been determined, most remain unidentified. Here, we used massively parallel reporter assays to identify [~]2,000 CREs across 27 dsDNA viruses from the Adenovirus, Herpesvirus, Polyomavirus and Papillomavirus families. Viral genomes have a higher CRE density than the human genome, with most viral CREs having promoter-like features and overlapping protein coding sequences. Using saturation mutagenesis and machine learning models, we report viral CRE regulators, including SP, ETS, bZIPs, and TFs acting downstream of signal-activated pathways. Altogether, we present a comprehensive functional CRE map of human-infecting dsDNA viruses that serves as a blueprint for further studies in viral regulation, reactivation, evolution, and viral vector design.

genomics↗