Biology subjects

Borges, L.

Publications and source records attributed to Borges, L..

6 recordsLinked to original sources

bioRxiv2026

Extending the MAD Toolbox: New Polymer Builder and Enhanced Martini Database

The MArtini Database (MAD) web server (https://mad.ens-lyon.fr/) has been updated with new tools, models, and capabilities to support a broader range of molecular systems for the Martini coarse-grained (CG) force field. The most notable addition is the MAD:Polymer Builder, enabling the automated construction of CG polymer models with varying architectures and complexities. The server now incorporates the latest developments in Martini 3, providing enhanced control within the MAD:Molecule Builder over the conversion of all-atom structures into CG representations, including the implementation of G[o]Martini 3 for protein complexes and water-protein interaction biases. The MAD:Polymer Builder and MAD:Molecule Builder are both adapted to work with intrinsically disordered proteins and domains. Substantial progress has been made in expanding the MAD:Database, making a growing library of Martini-ready compounds readily accessible across the entire MAD ecosystem. These advances position MAD as a comprehensive and evolving platform for the preparation of diverse systems in CG molecular simulations.

bioinformatics↗

bioRxiv2024

Early transatlantic movement of horses and donkeys at Jamestown

Domestic horses and donkeys played a key role in the initial colonization of the Atlantic seaboard of the Americas, a process partially chronicled by historical records. While Spanish colonists brought horses to the Caribbean and southern latitudes earlier, the transport of domestic horses to the English colony at Jamestown, Virginia in 1606 was among the first dispersals to the eastern seaboard. Archaeozoological analysis, isotope analysis, and radiocarbon dating of identifiable domestic equid remains from two contexts associated with the initial occupation of Jamestown demonstrate intense processing and consumption of the first Jamestown horses during the "Starving Time" winter of 1609, while paleopathological data show evidence of their use in transport. Osteological, genetic, and isotopic study of these equid remains reveal the presence of at least one adult domestic donkey with mixed European and West African ancestry, possibly supplied through undocumented exchange during a trans-Atlantic stopover. These results reveal the importance of equids in the survival of early European settlers and the global connectivity of early trans-Atlantic exchange in horses and donkeys, showing Caribbean and African links in the founding livestock populations and pointing towards an important and ecologically-anchored role for donkeys in the early colonial lifeways along the Eastern seaboard.

genetics↗

bioRxiv2023

Unraveling human hematopoietic progenitor cell diversity through association with intrinsic regulatory factors

Hematopoietic stem and progenitor cell (HSPC) transplantation is an essential therapy for hematological conditions, but finer definitions of human HSPC subsets with associated function could enable better tuning of grafts and more routine, lower-risk application. To deeply phenotype HSPCs, following a screen of 328 antigens, we quantified 41 surface proteins and functional regulators on millions of CD34+ and CD34- cells, spanning four primary human hematopoietic tissues: bone marrow, mobilized peripheral blood, cord blood, and fetal liver. We propose more granular definitions of HSPC subsets and provide new, detailed differentiation trajectories of erythroid and myeloid lineages. These aspects of our revised human hematopoietic model were validated with corresponding epigenetic analysis and in vitro clonal differentiation assays. Overall, we demonstrate the utility of using molecular regulators as surrogates for cellular identity and functional potential, providing a framework for description, prospective isolation, and cross-tissue comparison of HSPCs in humans.

cell biology↗

bioRxiv2022

Expression of terminal deoxynucleotidyl transferase (TdT) identifies lymphoid-primed progenitors in human bone marrow

Lymphoid specification in human hematopoietic progenitors is not fully understood. To better associate lymphoid identity with protein-level cell features, we conducted a highly multiplexed single-cell proteomic screen on human bone marrow progenitors. This screen identified terminal deoxynucleotidyl transferase (TdT), a specialized DNA polymerase intrinsic to VDJ recombination, broadly expressed within CD34+ progenitors prior to B/T cell emergence. While these TdT+ cells coincided with granulocyte-monocyte progenitor (GMP) immunophenotype, their accessible chromatin regions showed enrichment for lymphoid-associated transcription factor (TF) motifs. TdT expression on GMPs was inversely related to the SLAM family member CD84. Prospective isolation of CD84lo GMPs demonstrated robust lymphoid potential ex vivo, while still retaining significant myeloid differentiation capacity, akin to LMPPs. This multi-omic study identifies previously unappreciated lymphoid-primed progenitors, redefining the lympho-myeloid axis in human hematopoiesis.

immunology↗

bioRxiv2021

Integrating transcription factor abundance with chromatin accessibility in human erythroid lineage commitment

We present InTAC-seq, a method for simultaneous quantification of genome-wide open chromatin and intracellular protein abundance in fixed cells. Using InTAC we directly observe variation in chromatin accessibility and transcription factor motif occupancy driven by differences in transcription factor protein abundance. By purifying bone marrow progenitor cells based on GATA1 protein expression, we establish its role in both functional and epigenetic restriction of erythroid cell identity in human hematopoiesis.

genomics↗

bioRxiv2019

An integrated multi-omic single cell atlas to redefine human B cell memory

To evaluate the impact of heterogeneous B cells in health and disease, comprehensive profiling is needed at a single cell resolution. We developed a highly-multiplexed screen to quantify the co-expression of 351 surface molecules on low numbers of primary cells. We identified dozens of differentially expressed molecules and aligned their variance with B cell isotype usage, metabolism, biosynthesis activity, and signaling response. Here, we propose a new classification scheme to segregate peripheral blood B cells into ten unique subsets, including a CD45RB+ CD27- early memory population and a CD19hi CD11c+ memory population that is a potent responder to immune activation. Furthermore, we quantify the contributions of antibody isotype and cell surface phenotype to various cell processes and find that phenotype largely drives B cell function. Taken together, these findings provide an extensive profile of human B cell diversity that can serve as a resource for further immunological investigations.

immunology↗