Biology subjects

Garcia, A. D.

Publications and source records attributed to Garcia, A. D..

6 recordsLinked to original sources

bioRxiv2026

KIR*BLOOM: Accurate KIR genotyping using a new copy number-aware integrated genotype likelihood framework

Killer-cell immunoglobulin-like receptor (KIR) genes, key modulators of natural killer (NK) cell activity, play critical roles in immune response and disease susceptibility. Accurate KIR genotyping from short-read sequencing data remains challenging because of high sequence similarity among genes, extensive copy number variation, and substantial allelic diversity. Here, we present KIR*BLOOM, a likelihood-based approach for KIR genotyping from short-read data that models read depth and sequencing error across alternative genotype configurations. KIR*BLOOM first identifies KIR-relevant read pairs, maps them to a KIR allele database, and reduces the candidate allele space by excluding alleles unlikely to be present. It then infers gene copy number and selects alleles under the inferred copy-number constraints. Finally, variant calling is used to refine CDS sequences and identify potential novel alleles. We evaluated performance on 45 whole-genome sequencing samples with haplotype-resolved assemblies from the HPRC or HGSVC, using Immuannot-derived annotations as ground truth. KIR*BLOOM achieved 99.85% precision, 99.92% recall, and a Jaccard index of 99.77% for copy-number inference. At five-digit allele resolution, it achieved 92.73% precision, 92.69% recall, and an 87.29% Jaccard index, outperforming T1K, GraphKIR, and Geny. Together, these results demonstrate that KIR*BLOOM enables highly accurate KIR genotyping from short-read sequencing data.

bioinformatics↗

bioRxiv2025

Circuit specific specialization of human basal ganglia astrocytes

Astrocytes shape synapses and circuits, yet human basal ganglia astrocyte diversity is incompletely defined. We built a multimodal atlas by integrating single-nucleus RNA-sequencing and chromatin accessibility with DNA methylation, 3D chromatin conformation, and spatial transcriptomics, then mapped basal ganglia programs onto a whole-brain reference. Astrocytes segregated into three anatomical subgroups spanning striatal gray matter, extra-striatal gray matter, and white matter, with subgroup-biased neurotransmitter transporters and synapse-associated programs consistent with differences in dominant afferent input. Within striatum, dorsal and ventral astrocyte populations aligned with distinct microcircuits and were conserved in nonhuman primates. A deep learning sequence model identified subgroup-associated enhancer code and, when benchmarked against published enhancer-AAV datasets, supported the design of candidate viral tools to target basal ganglia astrocyte programs in vivo. Together, these data define major axes of human astrocyte specialization and provide a framework for cell type-specific dissection of basal ganglia function.

neuroscience↗

bioRxiv2025

Cross-species consensus atlas of the primate basal ganglia

The basal ganglia (BG) are conserved brain regions essential for motor control, learning, emotion, and cognition, and are implicated in neurological and psychiatric disease. Yet a unified cross-species taxonomy of BG cell types is lacking, limiting translation of BG circuit mechanisms, interpretation of human genetic risk, and development of cell type-targeted tools. We present a multiomic consensus atlas of 1.8 million nuclei from human, macaque, and marmoset spanning eight BG structures. Integrating cross-species gene expression, open chromatin, and spatial profiling enables definition of conserved and divergent cell types. Alignment to existing mouse and human atlases identifies 61 homologous cell types conserved over 80 million years. We identify a STRd D2 StrioMat Hybrid medium spiny neuron (MSN) type with molecular, electrophysiological, and morphological features that clarify hybrid MSN identities. Comparative cis-regulatory analysis reveals conserved sequence grammars that encode cell identity and inform viral targeting strategies, providing a foundational resource for BG evolution, function, and disease.

neuroscience↗

bioRxiv2025

A cross-species spatial transcriptomic atlas of the human and non-human primate basal ganglia

The basal ganglia are interconnected subcortical nuclei with complex topographical organization that orchestrate goal-directed behaviors and are implicated in neurodegenerative movement disorders. We generated a cellular-resolution, spatial transcriptomic atlas of the basal ganglia in human, rhesus macaque, and common marmoset, sampling over one million cells in each species. By integrating spatial data with a cross-species, consensus snRNA-seq cell type taxonomy, this atlas reveals conserved principles of molecular organization within and across structures. The cellular architecture is complex but highly stereotyped, with gene expression gradients superimposed onto discrete compartments. Extensive spatial sampling illuminates 3D gradients of molecular organization in the striatum and reveals cell type-specific core and shell compartments in the primate internal globus pallidus, which is conserved with mouse. This unified, cross-species spatial transcriptomic atlas will be a foundational resource for characterizing the molecular and functional organization of the basal ganglia and their roles in health and disease.

neuroscience↗

bioRxiv2022

Improving the efficacy and accessibility of intracranial viral vector delivery in non-human primates

Non-human primates (NHPs) are precious resources for cutting edge neuroscientific research, including large-scale viral vector-based experimentation such as optogenetics. We propose to improve surgical outcomes by enhancing surgical preparation practices of convection-enhanced delivery (CED), which is an efficient viral vector infusion technique for large brains such as NHPs. Here we present both real-time and next-day MRI data of CED in the brains of ten NHPs, and we present a quantitative, inexpensive, and practical bench-side model of the in vivo CED data. Our bench-side model is composed of food coloring infused into a transparent agar phantom, and the spread of infusion is optically monitored over time. Our proposed method approximates CED infusions into the cortex, thalamus, medial temporal lobe and caudate nucleus of NHPs, confirmed by MRI data acquired with either gadolinium-based or manganese-based contrast agents co-infused with optogenetic viral vectors. These methods and data serve to guide researchers and surgical team members in key surgical preparations for intracranial viral delivery using CED in NHPs, and thus improve expression targeting and efficacy and, as a result, reduce surgical risks.

neuroscience↗

bioRxiv2017

Abundance and diversity of the fecal resistome in slaughter pigs and broilers in nine European countries

EFFORT groupHaitske Graveland, Alieda van Essen, Bruno Gonzalez-Zorn, Gabriel Moyano, Pascal Sanders, Claire Chauvin, Julie David, Antonio Battisti, Andrea Caprioli, Jeroen Dewulf, Thomas Blaha, Katharina Wadepohl, Maximiliane Brandt, Dariusz Wasyl, Magdalena Skarzynska, Magdalena Zajac, Hristo Daskalov, Helmut W Saatkamp, Katharina D.C. Stark.\n\nAbstractAntimicrobial resistance (AMR) in bacteria and associated human morbidity and mortality is increasing. Use of antimicrobials in livestock selects for AMR that can subsequently be transferred to humans. This flow of AMR between reservoirs demands surveillance in livestock as well as in humans. As part of the EFFORT project (www.effort-against-amr.eu), we have quantified and characterized the acquired resistance gene pools (resistomes) of 181 pig and 178 poultry farms from nine European countries, generating more than 5,000 gigabases of DNA sequence, using shotgun metagenomics. We quantified acquired AMR using the ResFinder database and a database constructed for this study, consisting of AMR genes identified through screening environmental DNA. The pig and poultry resistomes were very different in abundance and composition. There was a significant country effect on the resistomes, more so in pigs than poultry. We found higher AMR loads in pigs, while poultry resistomes were more diverse. We detected several recently described, critical AMR genes, including mcr-1 and optrA, the abundance of which differed both between host species and countries. We found that the total acquired AMR level, was associated with the overall country-specific antimicrobial usage in livestock and that countries with comparable usage patterns had similar resistomes. Novel, functionally-determined AMR genes were, however, not associated with total drug use.

microbiology↗