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Taylor, K.

Publications and source records attributed to Taylor, K..

At least 19 recordsLinked to original sources
bioRxiv2026

FIDDL: depth-matched negative controls distinguish genuine interspecific introgression from competitive-mapping artifact

Interspecific introgression is routinely detected by competitively mapping reads to a concatenated multi-species reference and calling regions where a non-focal species recruits coverage. Using strains that cannot contain the ancestry being detected, we show this design generates substantial false-positive signal through two mechanisms with opposite phylogenetic-distance signatures. Standard nuclear assemblies omit the mitochondrion and 2-micron plasmid, leaving high-copy cytoplasmic reads without a legitimate target; completing the reference preferentially removes signal from the most divergent donor. Genuine cross-species sequence conservation inflates the most closely related donor. Masking chromosome ends removes its subtelomeric part but plateaus at a non-zero floor, and the interior residual traces to conserved single-copy genes where a short read carries under one base of discriminating information. The floor grows with sequencing depth (1.19% of callable positions at 50x, 2.02% at 147x, 3.85% at 393x in a pure strain), is not mitigated by long reads, and appears at sub-diploid dosage - three properties widely read as evidence of authenticity. Because the discriminating information is below single-read resolution, no read-level filter separates artifact from introgression; we show three that fail. What works is locus-level: a consensus-phylogenetic test (29/29 specificity on confirmed artifact) and an allele-fraction donor-match test, complementary and validated in both directions on independent published introgression. We package the comparative controls as FIDDL (False Introgression Detection via Depth-matched controls and Loci-recurrence), an open-source tool, withdraw two of our own analysis-ready calls, and show re-analysis of published wild isolates reduces low-confidence introgression by [~]53% while leaving high-confidence signal intact.

bioinformatics↗
bioRxiv2026

Genome-scale characterization of wild yeasts reveals cryptic diversity and population structure across three genera

Environmental surveys of wild yeasts typically rely on ribosomal barcodes, which cannot resolve cryptic species, interspecific gene flow, mixed cultures, or population structure. To determine what genome-scale characterization adds, we sequenced a representative panel of wild yeasts spanning the genera Saccharomyces, Schizosaccharomyces, and Lachancea using Oxford Nanopore long-read whole-genome sequencing and placed each isolate within published reference datasets. Whole-genome analyses revealed biologically important features that barcoding alone could not detect. A shagbark-hickory isolate resolved as a genuine two-species co-culture. An oak-bark isolate proved to be Schizosaccharomyces versatilis, a recently reinstated species represented by very few known strains, and its analysis demonstrated that standard assembly-quality benchmarks can be misleading for deep-branching taxa. Three Lachancea thermotolerans isolates formed a distinct, previously unsampled population within the wild tree-associated lineage, extending its known geographic range. In contrast, an apparent signal of Saccharomyces eubayanus introgression in two beer-associated S. cerevisiae isolates disappeared after analysis with matched negative controls and de novo assemblies, showing that it reflected mapping artifacts rather than genuine ancestry. Together, these results demonstrate that inexpensive long-read whole-genome sequencing transforms wild-yeast bioprospecting from species identification into a genome-scale framework for resolving cryptic diversity, population structure, and mixed cultures while providing stronger support - and stronger limits - for evolutionary inference. SIGNIFICANCEMost surveys of wild yeasts identify isolates using short DNA barcodes, which are well suited for naming species but often miss the evolutionary relationships and hidden diversity within them. By applying inexpensive whole-genome sequencing to a diverse collection of environmental yeasts, we uncovered previously undetected mixed cultures, a rare recently recognized species, and a distinct wild population, while also showing that an apparent case of interspecies gene exchange was instead a technical artifact. These results demonstrate that genome-scale analysis can both reveal biological diversity that simpler methods overlook and provide the evidence needed to avoid misleading evolutionary conclusions, making it a powerful new approach for studying natural microbial populations.

ecology↗
bioRxiv2026

Declaration of Fermentation: Community-Embedded Wild Yeast Bioprospecting as a Model for Place-Based CURE Design

Course-based undergraduate research experiences (CUREs) are widely recognized as a high-impact practice in biology education, yet most existing CURE frameworks treat the research organism as an interchangeable teaching prop rather than a genuine scientific contribution. We argue that place-based, community-embedded CUREs - in which students isolate, characterize, and publicly deploy a locally meaningful wild organism - constitute a qualitatively distinct model warranting broader adoption. As proof of concept, we present the Declaration of Fermentation project at Indiana University Bloomington: graduate researchers isolated a wild Saccharomyces cerevisiae strain from the bark of a campus landmark tree, confirmed its wild provenance by whole-genome sequencing and phylogenomics, and partnered with local craft breweries to produce a colonial-era inspired ale released publicly for the 250th anniversary of the Declaration of Independence. Volunteer sensory panels at two independent public tasting events (combined n = 33-34 per attribute) confirmed a fruity-funky profile consistent with wild-strain fermentation, with no significant differences between events (Mann-Whitney U, Benjamini- Hochberg-corrected p > 0.05 for all 11 attributes). We describe three design principles - genomically confirmed strain identity, mandatory community partnership, and place-based historical narrative - that distinguish this model from prior wild yeast brewing CUREs, discuss how these principles generalize to other institutions and fermentation vehicles, and identify next steps for formal learning assessment. Complete implementation protocols are provided as supplemental Appendices 1-6, and the bioinformatics pipeline is freely available at https://doi.org/10.5281/zenodo.20679384.

microbiology↗
bioRxiv2026

Vertical inhibition of the autophagy pathway impairs growth and enhances sensitivity to mTORC1 inhibition in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is dependent on autophagy for growth. Chloroquine/Hydroxychloroquine (CQ/HCQ), the sole FDA-approved autophagy inhibitors, have shown limited clinical efficacy as cancer therapies. To identify approaches to improve PDAC response to CQ, we performed a CQ-anchored, CRISPR-Cas9 mediated loss-of-function screen. We identified that the loss of genes encoding proteins upstream in the autophagy pathway enhanced CQ-mediated growth suppression. This indicated that simultaneous targeting of two distinct nodes of the same pathway, vertical inhibition, may be a more effective strategy than single node inhibition. We demonstrated that genetic loss or pharmacological inhibition of VPS34, a protein necessary for autophagosome nucleation, sensitized PDAC cells to inhibitors of the terminal stage of the autophagy pathway, including CQ and an inhibitor of PIKfyve. We extended this concept to the initiation complex and demonstrated that ULK1/2 inhibition synergized with CQ and PIKfyve inhibition to impair PDAC cell growth and increase apoptosis. Anticipating mechanisms of resistance to vertical autophagy inhibition, we performed reverse-phase protein array profiling and identified that vertical inhibition of the autophagy pathway resulted in enhanced activation of the PI3K-AKT-mTORC1 signaling pathway. Increased mTORC1 signaling resulted in heightened sensitivity to bi-steric mTORC1 inhibition in both cell line and organoid models of PDAC. This study identifies novel anti-autophagy inhibitor combinations that may improve the clinical efficacy of autophagy inhibition for PDAC treatment. IMPLICATIONSVertical inhibition of the autophagy pathway reduces pancreatic cancer cell growth, increases apoptosis, and enhances sensitivity to mTORC1 inhibition; thereby representing a novel therapeutic strategy for autophagy-driven pancreatic cancer.

Cancer Biology↗
bioRxiv2026

Myosin Filaments of Vertebrate Skeletal and Cardiac Muscle are Highly Similar, but not Identical

Striated muscles consist of two filament types, one composed mostly of actin and the other composed mostly of myosin1,2. Actin filaments are highly similar across different muscle types and species both invertebrate and vertebrate3. Myosin filaments of vertebrate striated muscle are quite homogeneous in structure having identical lengths, governed by the giant protein titin4,5, and rotational symmetries while varying mostly in the isoforms of its proteins. Conversely, myosin filaments from invertebrate striated muscle are highly heterogeneous in multiple ways even within a single organism. Myosin filaments from vertebrate cardiac muscle have been shown to be highly similar in structure between mice and humans6-8. Conversely, thick filaments from the highly specialized insect indirect flight muscle have been shown to be highly variable in structure9-14. Here we used the drug mavacamten to stabilize a myosin head conformation known as the interacting heads motif in a fast skeletal muscle of rabbits, a highly studied model system. We show that the structure of relaxed rabbit skeletal muscle thick filaments is highly similar to those of relaxed human and mouse cardiac muscle, differing primarily in the positioning of some domains of myosin binding protein C vis-a-vis titin. In the context of the very different structures from indirect flight muscle, the result highlights different solutions to the same problems, control of muscle force and the requirements of endothermy, the internal generation of heat. In mammals, thick filaments are poised for varying levels of myosin activation15, while indirect flight muscle is poised for narrowly defined, high frequency contraction. In mammals, endothermy is a continuous problem; in insects, endothermy is primarily necessary for flight16.

biophysics↗
bioRxiv2025

sEEG-Suite: An Interactive Pipeline for Semi-Automated Contact Localization and Anatomical Labeling with Brainstorm

Stereoelectroencephalography (sEEG) is a critical tool for mapping epileptic networks in patients with drug-resistant epilepsy. Accurate localization and labeling of sEEG contacts are essential for identifying the seizure onset zone (SOZ) and ensuring optimal resective surgery. Traditional methods for localizing and labeling sEEG contacts rely on manual processing, which is prone to human error and variability. To address these challenges, we developed and integrated a semi-automatic sEEG contact localization and labeling pipeline within Brainstorm1, an open-source software platform for multimodal brain imaging analysis2-8, widely adopted in the neuroscience community with over 50,000 registered users and an active online user forum. The software has been supported by the National Institute of Health (NIH) for over two decades. The pipeline presented in this paper performs three key steps: (1) import and apply rigid co-registration of post-implantation Computed Tomography (CT) or post-CT with pre-implantation Magnetic Resonance Imaging (pre-MRI), (2) post-CT image segmentation and semi-automatic detection of sEEG contacts using GARDEL9, which has been integrated as a Brainstorm plugin, and (3) automatic anatomical labeling of contacts using standard and commonly used brain anatomy templates and atlases. Integrating this pipeline into Brainstorm brings the best of both worlds: GARDELs automation and Brainstorms multimodal data compatibility, and rich library of visualization and advanced analysis tools at both sensor and source level6. This sEEG-Suite tool facilitates reproducible research, supports clinical workflows, and accelerates sEEG-based investigations of invasive brain recordings.

neuroscience↗
bioRxiv2025

Trans-ancestry Mendelian Randomization Discovers Novel Causal Genes for Autoimmune Disease Traits

Mendelian randomization (MR) using summary statistics from genome-wide association studies (GWAS) has become a powerful tool for dissecting the causal relationships between exposure and outcomes. As GWAS begins to incorporate samples of diverse ancestries, the optimal strategy to perform MR analysis integrating these GWAS results remains to be determined. To fill in this gap, we proposed a robust method that aggregates the genetic variant-risk factor association summary statistics of multiple ancestries by modelling the genetic effects of the exposure as a function of the principal components of genome-wide allele frequency. This allows borrowing information from different ancestry groups and accounting for potential between-ancestry heterogeneities. The method is general and can be used with different MR methods. We demonstrated that our method improves accuracy and power compared to the inverse-variance weighting method based on only ancestry-stratified samples, with additional benefits in correcting winners curse bias. We also illustrated the flexibility and potential of discovering novel causal genes for autoimmune disease traits of our method in practice.

genetics↗
bioRxiv2025

A CD57+ cytotoxic CD8 T cell subset associated with fibrotic lung disease in systemic sclerosis

Interstitial lung disease (ILD) is a major cause of morbidity and mortality in systemic sclerosis (SSc); however, the immunopathologic mechanisms driving lung disease in SSc are unclear. T cells have been implicated as a likely driver of lung injury in SSc. Here, we have evaluated T cells in blood and lungs of patients with SSc-ILD and identified a specific population of cytotoxic CD8 T cells that is expanded in SSc-ILD patients. Cytotoxic effector memory CD8 T cells marked by CD57 expression are preferentially expanded in SSc-ILD patients compared to SSc patients without ILD and controls and show prominent clonal expansion. These CD57+ T effector memory (TEM) cells differ from T effector memory cells re-expressing CD45RA (TEMRA) transcriptomically and functionally, with cytotoxic function that is enhanced by CD155 engagement of the costimulatory receptor CD226. Analyses of cells from ILD lungs indicate endothelial cells as a likely source of CD155 to activate CD57+ cytotoxic T cells. Together, the results implicate a CD57+ cytotoxic CD8 T cell population as a potential mediator of lung injury in SSc-ILD.

immunology↗
bioRxiv2025

Joint single-cell measurements of surface proteins, intracellular proteins and gene expression with icCITE-seq

The development of single-cell RNA-sequencing assays has transformed our understanding of cellular and tissue heterogeneity, yielding significant insights into disease biology and its underlying mechanisms. In this work, we describe icCITE-seq (intracellular cellular indexing of transcriptomes and epitopes), a scalable method that simultaneously measures surface and intracellular protein levels alongside gene expression across thousands of cells. We validate the specificity of intracellular staining and demonstrate the utility of this multi-omic approach in interrogating phenotypic cellular states through targeted genetic perturbations in primary human T cells. icCITE-seq enables systematic profiling of gene expression, coupled with cytoplasmic, nuclear and PTM epitopes, providing an integrated approach towards understanding cellular identity, complexity and disease regulatory mechanisms.

immunology↗
bioRxiv2023

DNA nicks in both leading and lagging strand templates can trigger break-induced replication

Encounters between replication forks and unrepaired single-strand DNA breaks (SSBs) generate single-ended double-strand breaks (seDSBs) that can later become double-ended (deDSBs) through fork convergence. seDSBs can be repaired by break-induced replication (BIR), which is a highly mutagenic pathway that is thought to be repsonsible for many of the mutations and genome rearrangements that drive cancer development. However, the frequency of BIRs deployment and its ability to be triggered by both leading and lagging template strand SSBs was unclear. Using site- and strand-specific SSBs generated by nicking enzymes, including CRISPR-Cas9n, we demonstrate that leading and lagging template strand SSBs in fission yeast are typically converted into deDSBs that are repaired primarily by error-free homologous recombination. However, both types of SSB can also trigger BIR, and the frequency of these events increases when the converging fork is delayed and the non-homologous end joining protein Ku70 is deleted.

molecular biology↗
bioRxiv2023

Lac-Phe mediates the anti-obesity effect of metformin

Metformin is a widely prescribed anti-diabetic medicine that also reduces body weight. The mechanisms that mediate metformins effects on energy balance remain incompletely defined. Here we show that metformin is a powerful pharmacological inducer of the anorexigenic metabolite Lac-Phe in mice as well as in two independent human cohorts. In cell culture, metformin drives Lac-Phe biosynthesis via inhibition of complex I, increased glycolytic flux, and intracellular lactate mass action. Other biguanides and structurally distinct inhibitors of oxidative phosphorylation also increase Lac-Phe levels in vitro. Genetic ablation of CNDP2, the principal biosynthetic enzyme for Lac-Phe, in mice renders animals resistant to metformins anorexigenic and anti-obesity effects. Mediation analyses also support a role for Lac-Phe in metformins effect on body mass index in humans. These data establish the CNDP2/Lac-Phe pathway as a critical mediator of the effects of metformin on energy balance.

physiology↗
bioRxiv2023

Variants in the DDX6-CXCR5 autoimmune disease risk locus influence the regulatory network in immune cells and salivary gland

Fine mapping and bioinformatic analysis of the DDX6-CXCR5 genetic risk association in Sjogrens Disease (SjD) and Systemic Lupus Erythematosus (SLE) identified five common SNPs with functional evidence in immune cell types: rs4938573, rs57494551, rs4938572, rs4936443, rs7117261. Functional interrogation of nuclear protein binding affinity, enhancer/promoter regulatory activity, and chromatin-chromatin interactions in immune, salivary gland epithelial, and kidney epithelial cells revealed cell type-specific allelic effects for all five SNPs that expanded regulation beyond effects on DDX6 and CXCR5 expression. Mapping the local chromatin regulatory network revealed several additional genes of interest, including lnc-PHLDB1-1. Collectively, functional characterization implicated the risk alleles of these SNPs as modulators of promoter and/or enhancer activities that regulate cell type-specific expression of DDX6, CXCR5, and lnc-PHLDB1-1, among others. Further, these findings emphasize the importance of exploring the functional significance of SNPs in the context of complex chromatin architecture in disease-relevant cell types and tissues.

genetics↗
bioRxiv2023

Proteome-Wide Association Studies for Blood Lipids and Comparison with Transcriptome-Wide Association Studies

Blood lipid traits are treatable and heritable risk factors for heart disease, a leading cause of mortality worldwide. Although genome-wide association studies (GWAS) have discovered hundreds of variants associated with lipids in humans, most of the causal mechanisms of lipids remain unknown. To better understand the biological processes underlying lipid metabolism, we investigated the associations of plasma protein levels with total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL) in blood. We trained protein prediction models based on samples in the Multi-Ethnic Study of Atherosclerosis (MESA) and applied them to conduct proteome-wide association studies (PWAS) for lipids using the Global Lipids Genetics Consortium (GLGC) data. Of the 749 proteins tested, 42 were significantly associated with at least one lipid trait. Furthermore, we performed transcriptome-wide association studies (TWAS) for lipids using 9,714 gene expression prediction models trained on samples from peripheral blood mononuclear cells (PBMCs) in MESA and 49 tissues in the Genotype-Tissue Expression (GTEx) project. We found that although PWAS and TWAS can show different directions of associations in an individual gene, 40 out of 49 tissues showed a positive correlation between PWAS and TWAS signed p-values across all the genes, which suggests a high-level consistency between proteome-lipid associations and transcriptome-lipid associations.

genomics↗
bioRxiv2023

Remote neuronal activity drives glioma infiltration via Sema4f

The tumor microenvironment (TME) plays an essential role in malignancy and neurons have emerged as a key component of the TME that promotes tumorigenesis across a host of cancers. Recent studies on glioblastoma (GBM) highlight bi-directional signaling between tumors and neurons that propagates a vicious cycle of proliferation, synaptic integration, and brain hyperactivity; however, the identity of neuronal subtypes and tumor subpopulations driving this phenomenon are incompletely understood. Here we show that callosal projection neurons located in the hemisphere contralateral to primary GBM tumors promote progression and widespread infiltration. Using this platform to examine GBM infiltration, we identified an activity dependent infiltrating population present at the leading edge of mouse and human tumors that is enriched for axon guidance genes. High-throughput, in vivo screening of these genes identified Sema4F as a key regulator of tumorigenesis and activity-dependent infiltration. Furthermore, Sema4F promotes the activity-dependent infiltrating population and propagates bi-directional signaling with neurons by remodeling tumor adjacent synapses towards brain network hyperactivity. Collectively, our studies demonstrate that subsets of neurons in locations remote to primary GBM promote malignant progression, while revealing new mechanisms of tumor infiltration that are regulated by neuronal activity.

cancer biology↗
bioRxiv2023

Glutathione supports lipid abundance in vivo

Cells rely on antioxidants to survive. The most abundant antioxidant is glutathione (GSH). The synthesis of GSH is non-redundantly controlled by the glutamate-cysteine ligase catalytic subunit (GCLC). GSH imbalance is implicated in many diseases, but the requirement for GSH in adult tissues is unclear. To interrogate this, we developed a series of in vivo models to induce Gclc deletion in adult animals. We find that GSH is essential to lipid abundance in vivo. GSH levels are reported to be highest in liver tissue, which is also a hub for lipid production. While the loss of GSH did not cause liver failure, it decreased lipogenic enzyme expression, circulating triglyceride levels, and fat stores. Mechanistically, we found that GSH promotes lipid abundance by repressing NRF2, a transcription factor induced by oxidative stress. These studies identify GSH as a fulcrum in the livers balance of redox buffering and triglyceride production.

biochemistry↗
bioRxiv2022

TCID50 Measurements of anti-viral efficacy on metal printed masks and plastic surfaces

The SARS-CoV-2 pandemic has created a need for effective personal protective equipment (PPE) to prevent viral spread. PPE like face masks contain the spread of virus-filled droplets and thus reduce infection rates, has been a critical tool in stopping the spread of SARS-CoV-2. PET plastic barriers have also been used in public settings to reduce face to face viral transmission. However, in some cases, they have provided additional contact with the virus due to contamination. In order study, we evaluated the effectiveness of face masks and PET plastics coated in different metals in reducing viral load. We compared PPE printed with silver, copper, or zinc for their ability to inactivate live human coronavirus HCoV 229E. Our results show that silver and copper have significant anti-viral efficacy when printed on nonwoven fabric compared to the controls. The metal-printed PET showed around 70% anti-viral efficacy with any formulations, with copper performing the best. This work builds more data to support the development of metal printed materials for enhanced protection against coronaviruses.

bioengineering↗
bioRxiv2022

Inflammatory mediators act at renal pericytes to elicit contraction of vasa recta and reduce pericyte density along this medullary vascular network

Regardless of initiating cause, renal injury promotes a potent pro-inflammatory environment in the outer medulla and a concomitant sustained decrease in medullary blood flow (MBF). This decline in MBF is believed to one of the critical events in the pathogenesis of acute kidney injury (AKI), yet the precise cellular mechanism underlying this are still to be fully elucidated. MBF is regulated by contractile pericyte cells that reside on the descending vasa recta (DVR) capillaries, which are the primary source of blood flow to the medulla. Using the rodent and murine live kidney slice models, we sought to investigate the acute effects of key medullary inflammatory mediators TNF-, IL-1{beta}, IL-33, IL-18, C3a and C5a on vasa recta pericytes. Live kidney slices taken from both mice and rats and exposed to TNF-, IL-18, IL-33, and C5a demonstrated a real-time pericyte-mediated constriction of DVR. When pro-inflammatory mediators were applied in the presence of the AT1-R blocker Losartan the inflammatory-mediated constriction that had previously been observed was significantly attenuated. When live kidney slices were exposed to inflammatory mediators for 4-hours, we noted a significantly reduction in the number of NG2+ positive pericytes along vasa recta capillaries in both rodent and murine kidney slices. Data collected in this study, demonstrate that inflammatory mediators can dysregulate pericytes to constrict DVR diameter and reduce the density of pericytes along vasa recta vessels, further diminishing the regulatory capacity of the capillary network. We postulate that preliminary findings here suggest pericytes play a role in AKI. New & NoteworthyHow medullary blood flow (MBF) becomes disproportionately dysregulated following renal injury is poorly understood yet is associated with worse prognostic outcomes following AKI. This study shows in both rats and mice that inflammatory mediators associated with AKI have acute and sustained microvascular actions at pericytes eliciting dysregulation of descending vasa recta (DVR) diameter and their loss from the DVR. This work highlights a possible pathology behind the dysregulation and reduction of MBF observed following AKI.

physiology↗