Biology subjects

Batista, T. M.

Publications and source records attributed to Batista, T. M..

4 recordsLinked to original sources

bioRxiv2026

Metabolic disease-relevant stimuli unmask context-dependent genetic regulation of cardiometabolic loci in human adipocytes

Genome-wide association studies (GWAS) have identified thousands of loci associated with cardiometabolic disease, yet translating these associations into regulatory mechanisms, effector genes, and cellular programs remains a major challenge. A key limitation is that genetic effects are often highly context dependent, varying across cell states and environmental conditions that are difficult to model at scale. Here, we leverage CellGenBank, a population-scale biobank of primary human adipose-derived mesenchymal stem cells (AMSCs), to implement a multi-donor cell village in vitro system to map cardiometabolic disease genetic variation across adipocyte differentiation and metabolic stress conditions. We pooled AMSCs from 118 donors into multiplexed villages, differentiated them toward adipocytes, and profiled chromatin accessibility and gene expression using single-nucleus multiome sequencing under four disease-relevant conditions: basal, elevated free fatty acids, low glucose, and hypoxia. By combining with genetic demultiplexing, we quantify how regulatory element activity, gene expression, and higher-order cellular programs are modulated by both genotype and environmental context. Across conditions, we identify widespread context-specific cis-regulatory effects, including expression and chromatin accessibility quantitative trait loci that are masked in baseline states. Genetic effects frequently converge on coordinated transcriptional programs linked to lipid metabolism, insulin responsiveness, and stress adaptation, enabling the identification of cellular program QTLs that bridge variants, genes, and disease-relevant phenotypes. Integration with cardiometabolic GWAS reveals enhanced colocalization in condition- and state-resolved analyses, highlighting the importance of modeling environmental context to resolve disease mechanisms. Together, our study establishes large-scale adipocyte cell villages as a powerful and generalizable framework to map the context-dependent regulatory architecture of cardiometabolic disease and provides a resource linking human genetic variation to adipocyte cellular programs.

genomics↗

bioRxiv2025

The peptide LyeTx I mnΔK induces transcriptomic reprogramming in a novel Multidrug-resistant Acinetobacter baumannii

Acinetobacter baumannii is a critical pathogen in healthcare-associated infections, and treatment is challenging due to the emergence of multidrug-resistant strains. Antimicrobial peptides, such as LyeTx I mn{Delta}K, a synthetic peptide derived of a toxin from the spider Lycosa erythrognatha, represent a promising alternative due to their broad-spectrum activity and synergistic potential with antibiotics like meropenem. This study aimed to compare the genomes of several A. baumannii strains, including a novel multidrug-resistant A. baumannii isolate (AC37), and to evaluate the antimicrobial effects of LyeTx I mn{Delta}K-alone and in combination with meropenem-through transcriptomic analysis. Genome assembly and annotation of AC37 revealed 31 antibiotic resistance genes, and phylogenetic analysis comprising 123 A. baumannii genomes, including the reference strain, identified three unique resistant genes in the AC37 strain. Mobilome analysis showed 13 genes associated with mobile genetic elements, including two of the unique genes, highlighting horizontal gene transfer events. Transcriptomic profiling revealed that treatment with LyeTx I mn{Delta}K peptide alone induced several differentially expressed genes, including two efflux pump operons. Additionally, pathways related to protein synthesis, export, and secretion were activated, indicating a broader cellular response to the peptide. The treatment with LyeTx I mn{Delta}K in combination with meropenem disrupted oxidative phosphorylation, further revealing the metabolic plasticity of the bacterial response to external stresses. This study characterizes a new A. baumannii isolate and provides new insights into the bacterial response to a potential novel therapeutic molecule.

bioinformatics↗

bioRxiv2025

Retroelement expansions underlie genome evolution in stingless bees

Stingless bees are essential pollinators and emerging models for studying behavioral and genomic evolution. In the genus Melipona, a major difference in heterochromatin organization defines two groups: Group I species (e.g., M. quadrifasciata) with <50% of pericentromeric heterochromatin and Group II species (e.g., M. scutellaris) containing >50% heterochromatin across their chromosomes. These differences are thought to correlate with genome size and transposable element (TE) content, offering a unique opportunity to explore how heterochromatin variation, TE dynamics, and chromosomal evolution interact in a phylogenetic context. We present pseudo-chromosome-level genome assemblies for M. quadrifasciata and M. scutellaris obtained by long-read sequencing and Hi-C scaffolding. Comparative analyses reveal conserved synteny but marked divergence in structural variants and TEs. M. scutellaris shows an expansion of retrotransposons, particularly Gypsy/DIRS1 elements, concentrated in TE hotspots linked to chromosomal rearrangements and structural variants. This coincides with distinct methylation entropy and an expansion of histone deacetylase orthologs, potentially affecting heterochromatin organization. The increased ratio of retrotransposons in M. scutellaris is counterbalanced by more DNA transposons in M. quadrifasciata, resulting in genomes of similar overall sizes but of distinct heterochromatin distribution. Advancing our understanding of genome evolution in eusocial insects, we provide high-resolution genomic resources for two Melipona species that differ in heterochromatin content. Our results highlight the complex role of TEs in shaping genomes and underscore their influence on chromosomal and epigenetic innovation, providing strong evidence that TE dynamics underly the striking heterochromatic differences observed in Melipona.

genomics↗

bioRxiv2023

A genome-wide atlas of human cell morphology

A key challenge of the modern genomics era is developing data-driven representations of gene function. Here, we present the first unbiased morphology-based genome-wide perturbation atlas in human cells, containing three genome-scale genotype-phenotype maps comprising >20,000 single-gene CRISPR-Cas9-based knockout experiments in >30 million cells. Our optical pooled cell profiling approach (PERISCOPE) combines a de-stainable high-dimensional phenotyping panel (based on Cell Painting1,2) with optical sequencing of molecular barcodes and a scalable open-source analysis pipeline to facilitate massively parallel screening of pooled perturbation libraries. This approach provides high-dimensional phenotypic profiles of individual cells, while simultaneously enabling interrogation of subcellular processes. Our atlas reconstructs known pathways and protein-protein interaction networks, identifies culture media-specific responses to gene knockout, and clusters thousands of human genes by phenotypic similarity. Using this atlas, we identify the poorly-characterized disease-associated transmembrane protein TMEM251/LYSET as a Golgi-resident protein essential for mannose-6-phosphate-dependent trafficking of lysosomal enzymes, showing the power of these representations. In sum, our atlas and screening technology represent a rich and accessible resource for connecting genes to cellular functions at scale.

genomics↗