Biology subjects

Vasseur, D.

Publications and source records attributed to Vasseur, D..

8 recordsLinked to original sources

bioRxiv2026

Bridging physiological responses to population outcomes under variable thermal stress

Embedding thermal tolerance metrics into population dynamics offers a promising toolkit for understanding the impacts of stressful heat events, but the time-dependence of thermal stress rarely factors into such assessments. Within organisms, heat causes damage that alternatively accumulates under stressful temperatures and is repaired under permissive ones. While risk under exclusively stressful temperatures is well characterized by thermal death time models, resilience to fluctuating temperatures is less clear. Understanding how this damage accumulation within organisms scales up to affect population thermal tolerance is a necessary step for predicting population dynamics and extinction risk. We address this gap by embedding a model of organismal stress and recovery into population dynamics, yielding time-dependent thermal performance curves of population growth rates. By parameterizing this novel framework with existing data from Drosophila melanogaster, we explore how integrating thermal stress across biological scales shapes the consequences of organismal stress on population outcomes under realistic thermal fluctuations.

ecology↗

bioRxiv2026

Dormancy stabilizes structured food webs

Theory predicts that strong species interactions drive ecological instability, but strong interactions are common in ecosystems while strong instability appears rare. This discrepancy motivates enduring interest in ecological mechanisms that limit or counteract instability. Dormancy - reversible metabolic suppression - may be one. Dormancy is a ubiquitous life history trait found in organisms ranging from bacteria to trees. Dormant individuals form "seed banks" that are temporarily disengaged from demographic processes and species interactions, creating a memory of past ecological dynamics. Seed banks can stabilize predator-prey interactions, but whether, when, and how they affect the stability of larger ecological networks is uncertain. We show that dormancy stabilizes oscillatory dynamics in a minimal mathematical model and illustrate how dormancy converts high oscillation frequency into strong restoring force. We find that dormancy can have qualitative stabilizing effects in structured food webs that undergo Hopf bifurcations and exhibit oscillatory instability, but not in unstructured networks or those dominated by competitive or mutualistic interactions. This classification remains accurate when only a subset of species go dormant and drive stabilization. Our results clarify when dormancy can promote stability, indicating that dormancy may be an important but overlooked stabilizing factor in food webs.

ecology↗

bioRxiv2026

Transcription Factor Subtype Governs Response and Resistance to DLL3-Directed T-Cell Engagement in Small Cell Lung Cancer

Although small cell lung cancer (SCLC) comprises transcription factor (TF)-defined molecular subtypes (ASCL1, NEUROD1, POU2F3), the extent to which these subtypes predict response to clinically effective therapy in patients--and whether therapy can select for subtype switching--remains unknown. The recent approval of the DLL3xCD3 bispecific T-cell engager tarlatamab represents one of the first meaningful advances in relapsed small cell lung cancer (SCLC) in decades, yet responses remain heterogeneous and resistance is inevitable. Here, we inferred SCLC gene expression from circulating chromatin in prospectively collected patient plasma (46 patients; 167 samples), enabling interrogation of response and acquired resistance to tarlatamab. Parallel development of the first immunocompetent syngeneic mouse model to study tarlatamab response and resistance enabled functional validation. Across species, findings converged on a central principle: TF subtype governs both initial response and acquired resistance. Therapeutic response was significantly associated with ASCL1-subtype tumors, whereas NEUROD1-subtype tumors exhibited inferior responses and POU2F3-subtype tumors were uniformly resistant, consistent with DLL3 being a direct ASCL1 transcriptional target and most highly expressed in ASCL1-positive tumors. Strikingly, one mode of acquired resistance revealed therapeutic selection for a NEUROD1-high state with concomitant DLL3 downregulation. Other resistant tumors exhibited enrichment of regulatory and exhausted T-cell programs, highlighting tarlatamabs dual-targeting mechanism of action. Together, these results reveal that tarlatamab exerts selective pressure against ASCL1-driven lineages, facilitating resistance through loss of an antigen intrinsically linked to that state. These findings underscore the clinical relevance of TF-defined molecular subtypes in human SCLC. More broadly, they highlight the power of integrating longitudinal in vivo plasma transcriptional profiling from patient plasma with functional mouse modeling to uncover clinical and biological mechanisms of response and resistance to cell-surface-targeted therapies.

cancer biology↗

bioRxiv2026

Temperature-dependent performance scales with maximum heat tolerance across ectotherms

Projecting species responses to changing temperatures remains a major challenge in ecology. Central to this effort is harnessing our understanding of species thermal physiological traits, which underlie ectotherm fitness. These traits are typically characterized by describing performance across temperatures (thermal performance curve, TPC), and/or tolerance limits, which capture endpoints of biological failure. Despite their importance, we still lack an understanding of the functional relationship between these traits, limiting our ability to integrate them into comprehensive vulnerability assessments. Using a synthesized dataset of >100 ectotherms, we tested how heat tolerance (CTmax) relates to key TPC traits: thermal optima, thermal maxima, and the supra-optimal range of temperatures where performance is positive. Across taxa, TPC traits were positively related to CTmax, demonstrating a link between heat tolerance and temperature-dependent performance at sub-critical temperatures. While acute locomotor performance scaled proportionally with CTmax, metabolic processes and sustained locomotion scaled sub-proportionally, suggesting decoupling of CTmax and performance among high-CTmax species. This suggests that using CTmax as a comparative metric may overestimate thermal safety margins for metabolic processes critical to growth. Our results indicate that while CTmax and TPCs reflect shared underlying constraints--particularly in acute neuro-muscular traits--their relationship is dependent on timescale and the TPC response trait. Our findings connect our understanding of the processes that maintain performance over thermal gradients with those that cause performance to fail, improving our ability to project species persistence in a warming world. SignificanceClimate warming is increasingly reshaping the thermal environments that govern species persistence worldwide. Predicting vulnerability requires integrating multiple aspects of thermal biology, yet relationships among widely used thermal traits remain poorly understood. By synthesizing data from more than 100 ectotherm species, we quantify links between acute heat tolerance and traits describing sustained biological function across temperatures. We show that performance at relatively benign temperatures and performance at thermal extremes are coupled, but this coupling is strongly process and timescale dependent, with close correspondence for short term locomotion but weaker coupling for metabolic processes. Our results link the processes that maintain performance across temperatures with those that cause failure, fundamentally advancing our projections of species performance in a warming world.

ecology↗

bioRxiv2026

Integrated inference of cancer gene expression from cell-free plasma chromatin

Gene expression is a defining determinant of tumor identity, behavior, and therapeutic response, yet remains challenging to measure noninvasively. Here, we introduce APEX (Associating Plasma Epigenomic features with eXpression), a framework for inferring expression from circulating cell-free chromatin. Trained on [~]270,000 gene-sample pairs from matched tumor RNA-seq and plasma cfChIP-seq across multiple cancers and validated on >15 unseen cancer subtypes, APEX accurately infers cancer gene expression across a range of tumor fractions and outperforms existing plasma-based approaches by integrating positional histone mark and DNA fragmentation patterns across promoters and gene bodies. Using plasma alone, APEX enables classification of prognostically relevant basal and classical pancreatic cancer subtypes and identifies plasma-inferred NECTIN4 expression as a biomarker of response to enfortumab vedotin in metastatic bladder cancer. Together, these findings establish APEX as a biopsy-free approach for profiling tumor transcriptional states and extend liquid biopsy beyond genomic alterations to clinically relevant gene expression programs.

genomics↗

bioRxiv2025

SNAP: Streamlined Nextflow Analysis Pipeline for Immunoprecipitation-Based Epigenomic Profiling of Circulating Chromatin

Epigenomic profiling of circulating chromatin is a powerful and minimally invasive approach for detecting and monitoring disease, but there are no bioinformatics pipelines tailored to the unique characteristics of cell-free chromatin. We present SNAP (Streamlined Nextflow Analysis Pipeline), a reproducible, scalable, and modular workflow specifically designed for immunoprecipitation-based methods for profiling cell-free chromatin. SNAP incorporates quality control metrics optimized for circulating chromatin, including enrichment score and fragment count thresholds, as well as direct estimation of circulating tumor DNA (ctDNA) content from fragment length distributions. It also includes SNP fingerprinting to enable sample identity verification. When applied to cfChIP-seq and cfMeDIP-seq data across multiple cancer types, SNAPs quality filters significantly improved classification performance while maintaining high data retention. Independent validation using plasma from patients with osteosarcoma confirmed the detection of tumor-associated epigenomic signatures that correlated with ctDNA levels and reflected disease biology. SNAPs modular architecture enables straightforward extension to additional cell-free immunoprecipitation-based assays, providing a robust framework to support studies of circulating chromatin broadly. SNAP is compatible with cloud and high-performance computing environments and is publicly available at https://github.com/prc992/SNAP/. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/694452v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@47c734org.highwire.dtl.DTLVardef@674af8org.highwire.dtl.DTLVardef@16ae938org.highwire.dtl.DTLVardef@1f57a01_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2023

Interactions between temperature and nutrients determine the population dynamics of primary producers

Global change is rapidly and fundamentally altering many of the processes regulating the flux of energy throughout ecosystems and although researchers now understand the effect of temperature on key rates (such as aquatic primary productivity), the theoretical foundation needed to generate forecasts of biomass dynamics and extinction risk remains underdeveloped. We develop new theory that describes the interconnected effects of nutrients and temperature on phytoplankton populations and show that the thermal response of equilibrium biomass (i.e., carrying capacity) always peaks at a lower temperature than for productivity (i.e., growth rate). This difference results from trade-offs between the thermal responses of growth, death, and per-capita impact on the nutrient pool, making this thermal mismatch highly general and applicable to widely used population models. We further show that non-equilibrium dynamics depend on the pace of environmental change relative to underlying vital rates, and that populations respond to variable environments differently at high vs. low temperatures due to thermal asymmetries.

ecology↗

bioRxiv2018

Beta diversity patterns derived from island biogeography theory

The Theory of Island Biogeography (TIB) has been successful in predicting alpha diversity patterns such as species-area relationships and species-abundance distributions. Although beta diversity (i.e. the dissimilarity of community composition) has long been recognized as an important element of the TIB and is crucial for understanding community assembly processes, it has never been formally incorporated into the theory. Here we derive theoretical predictions for the expected pairwise beta diversity values under a species-level neutral scenario where all species have equal colonization and extinction rates. We test these predictions for the avian community composition of 42 islands (and 93 species) in the Thousand Island Lake, China. We find that alpha diversity patterns alone do not distinguish a species-level neutral model from a non-neutral model. In contrast, beta diversity patterns clearly reject a species-level neutral model. We suggest that the presented theoretical integration beta diversity offers a powerful path for testing the presence of neutral processes in ecology and biogeography.

ecology↗