Biology subjects

Mudge, J.

Publications and source records attributed to Mudge, J..

9 recordsLinked to original sources

bioRxiv2026

Genomes of three Sympatric Species of an Adaptive Radiation: Cyprinodon variegatus, C. desquamator, and C. brontotheroides

Speciation is a central process in evolutionary biology that involves the formation of reproductive barriers between diverging populations. This process can occur through multiple ecological, behavioral, and genetic mechanisms that ultimately lead to changes within a population leading to the formation of distinct species. The relatively young adaptive radiation of Cyprinodon pupfishes in the lakes of San Salvador Island provides a powerful system to study the drivers of speciation in species that exist both sympatrically and allopatrically. The three species; C. variegatus, C. desquamator, and C. brontotheroides, can be found in many lakes on the island, exhibit distinct morphological adaptations relating to feeding, and, when in sympatry, the three species have overlapping habitats and breeding grounds. Species boundaries are maintained by asymmetric mate choice by both males and females, which reinforce extreme fitness costs of hybridization. Here we present high-quality annotated reference genomes for these three species generated using PacBio hifi sequencing. The assemblies resulted in a genome size of approximately 1.2 Gb for each species with most sequences scaffolding into 24 chromosomes with BUSCO analysis indicating a >99% level of completion. The annotation of these three genomes generated over 21,500 protein coding genes with BUSCO analysis indicating a >86 completion. These genomes provide a key resource for studying the genomic architecture of ecological specialization, reproductive isolation in sympatry, and rapid speciation and will facilitate future comparative and population genomic studies on adaptive radiations.

genomics↗

bioRxiv2026

Haplotype-resolved genome of autotetraploid alfalfa (Medicago sativa) Regen-SY27x uncovers large scale structural variation and resistance gene dynamics

Polyploid genome assembly presents unique challenges due to extensive heterozygosity and complex haplotype structure. We report a haplotype-resolved, chromosome-scale assembly of Regen-SY27x, a genotype of autotetraploid alfalfa (Medicago sativa), which is widely used for genetic modification because of its excellent regenerative capacity in tissue culture. Using PacBio HiFi long reads, Omni-C scaffolding, and linkage map guided phasing, we generated a 3.2 GB assembly comprising four haplotypes with high contiguity and completeness. Kmer-based validation confirmed accurate haplotype separation, while linkage map integration and dotplot analysis identified and corrected chimeric scaffolds. Gene annotation yielded 221,688 protein-coding genes, with more than 99% assigned to pseudochromosomes. Repetitive elements accounted for 62.7% of the genome, dominated by long terminal repeat retrotransposons and a high fraction of Helitrons. The spatial enrichment of Helitrons within gene-dense distal chromosome arms underscores their pivotal role as key drivers of genomic innovation and gene family expansion. We identified 3,696 nucleotide-binding leucine-rich repeat R genes, with Toll/interleukin-1 receptor-like and Rx-type subclasses forming large tandem clusters across haplotypes. Comparative analyses revealed strong macrosyntenic conservation among Regen-SY27x and the publicly available Chinese alfalfa genomes but extensive structural variation both within Regen-SY27x haplotypes and between Regen-SY27x and the Chinese genotypes with tens of thousands of duplications, inversions, and translocations detected. These results demonstrate that a single autotetraploid individual captures extensive structural diversity, but individuals from different populations vary greatly. The Regen-SY27x assembly provides a foundational genomic resource for investigating polyploid genome evolution and identifying genetic variation relevant to biological and agronomic improvement in alfalfa. Article SummaryThis study presents the first chromosome-scale, haplotype-resolved genome assembly of the US alfalfa germplasm, Regen-SY27x, a key alfalfa genotype used widely for genetic engineering. We integrated HiFi long reads, Omni-CTM scaffolding, and linkage map-guided phasing to reconstruct all four haplotypes of this complex autotetraploid. Our results identified 221,688 protein-coding genes and reveal immense intra-individual structural variations dominated by small duplications. This high-quality reference serves as a foundational tool for the alfalfa community, enabling researchers to link complex structural diversity with agronomic traits and further enhance the biotechnological potential of this essential forage crop.

genomics↗

bioRxiv2026

PanACRpred: Predicting Accessible Chromatin Regions in Pangenomes using Motif Chaining

In this work, we investigate using motif subsequence features to predict whether a genomic region is accessible to regulatory proteins, i.e. an accessible chromatin region (ACR), enabling transcription of associated genes. We focus on plants, whose agricultural and ecological importance make them interesting and important organisms to study, and whose complex genomes provide important stress tests for our algorithm. We show that motif sequence similarity as found by co-linear chaining can be used in combination with machine learning models to effectively predict ACRs in genome assemblies.

bioinformatics↗

bioRxiv2025

An expanded reference catalog of translated open reading frames for biomedical research

Non-canonical (i.e., unannotated) open reading frames (ncORFs) have until recently been omitted from reference genome annotations, despite evidence of their translation, limiting their incorporation into biomedical research. To address this, in 2022, we initiated the TransCODE consortium and built the first community-driven consensus catalog of human ncORFs, which was openly distributed to the research community via Ensembl-GENCODE. While this catalog represented a starting point for reference ncORF annotation, major technical and scientific issues remained. In particular, this initial catalogue had no standardized framework to judge the evidence of translation for individual ncORFs. Here, we present an expanded and refined catalog of the human reference annotation of ncORFs. By incorporating more datasets and by lifting constraints on ORF length and start-codon, we define a comprehensive set of 28,359 ncORFs that is nearly four times the size of the previous catalog. Furthermore, to aid users who wish to work with ncORFs with the strongest and most reproducible signals of translation, we utilized a data-driven framework (i.e. translation signature scores) to assess the accumulated evidence for any individual ncORF. Using this approach, we derive a subset of 7,888 ncORFs with translation evidence on par with canonical protein-coding genes, which we refer to as the Primary set. This set can serve as a reliable reference for downstream analyses and validation, with a particular emphasis on high quality. Overall, this update reflects continual community-driven efforts to make ncORFs accessible and actionable to the broader research public and further iterations of the catalog will continue to expand and refine this resource.

genomics↗

bioRxiv2021

Augmented Transcutaneous Stimulation Using an Injectable Electrode

Minimally invasive neuromodulation technologies seek to marry the neural selectivity of implantable devices with the low-cost and non-invasive nature of transcutaneous electrical stimulation (TES). The Injectrode(R) is a needle-delivered electrode that is injected onto neural structures under image guidance. Power is then transcutaneously delivered to the Injectrode using surface electrodes. The Injectrode serves as a low-impedance conduit to guide current to the deep on-target nerve, reducing activation thresholds by an order of magnitude compared to using only surface stimulation electrodes. To minimize off-target recruitment of cutaneous fibers, the energy transfer efficiency from the surface electrodes to the Injectrode must be optimized. TES energy is transferred to the Injectrode through both capacitive and resistive mechanisms. Electrostatic finite element models generally used in TES research consider only the resistive means of energy transfer by defining tissue conductivities. Here, we present an electroquasistatic model, taking into consideration both the conductivity and permittivity of tissue, to understand transcutaneous power delivery to the Injectrode. The model was validated with measurements taken from (n=4) swine cadavers. We used the validated model to investigate system and anatomic parameters that influence the coupling efficiency of the Injectrode energy delivery system. Our work suggests the relevance of electroquasistatic models to account for capacitive charge transfer mechanisms when studying TES, particularly when high-frequency voltage components are present, such as those used for voltage-controlled pulses and sinusoidal nerve blocks.

bioengineering↗

bioRxiv2021

Multi-tissue integrative analysis of personal epigenomes

Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on a single haploid reference genome. Here, we present the EN-TEx resource of personal epigenomes, for [~]25 tissues and >10 assays in four donors (>1500 open-access functional genomic and proteomic datasets, in total). Each dataset is mapped to a matched, diploid personal genome, which has long-read phasing and structural variants. The mappings enable us to identify >1 million loci with allele-specific behavior. These loci exhibit coordinated epigenetic activity along haplotypes and less conservation than matched, non-allele-specific loci, in a fashion broadly paralleling tissue-specificity. Surprisingly, they can be accurately modelled just based on local nucleotide-sequence context. Combining EN-TEx with existing genome annotations reveals strong associations between allele-specific and GWAS loci and enables models for transferring known eQTLs to difficult-to-profile tissues. Overall, EN-TEx provides rich data and generalizable models for more accurate personal functional genomics.

genomics↗

bioRxiv2020

Loss of KHSRP Increases Neuronal Growth and Synaptic Transmission and Alters Memory Consolidation Through RNA Stabilization

The KH-type splicing regulatory protein (KHSRP) is an RNA-binding protein linked to decay of AU-rich element containing mRNAs. We have previously shown that KHSRP destabilizes the mRNA encoding the growth-associated protein GAP-43 and decreases neurite growth in cultured embryonic neurons. In contrast, loss of KHSRP stabilizes Gap43 mRNA and increases neurite growth. Here, we have tested functions of neural KHSRP in vivo. We find upregulation of 1460 mRNAs in the neocortex of adult Khsrp-/- mice, of which 527 bind to KHSRP with high specificity. These KHSRP targets are involved in pathways for neuronal morphology, axon guidance, neurotransmission and long-term memory. Neocortical neurons show increased axon growth and dendritic spine density in Khsrp-/- mice. Analyses of neuronal cultures from embryonic Khsrp-/- mice point to a neuron-intrinsic alteration in axonal and dendritic growth and elevations in KHSRP-target mRNAs, including subcellularly localized mRNAs. Hippocampus and infralimbic cortex of Khsrp-/- mice show presynaptic elevations in neurotransmission. The Khsrp-/- mice have significant deficits in both trace conditioning and attention set-shifting tasks compared Khsrp+/+ mice, indicating impaired prefrontal- and hippocampal-dependent memory consolidation with loss of KHSRP. Overall, our results indicate that prenatal deletion of KHSRP impairs neuronal development resulting in alterations in neuronal morphology and function by changing post-transcriptional control of neuronal gene expression.

neuroscience↗

bioRxiv2019

Optimal sample size calculation for null hypothesis significance tests

Traditional study design tools for estimating appropriate sample sizes are not consistently used in ecology and can lead to low statistical power to detect biologically relevant effects. We have developed a new approach to estimating optimal sample sizes, requiring only three parameters; a maximum acceptable average of and {beta}, a critical effect size of minimum biological relevance, and an estimate of the relative costs of Type I vs. Type II errors.This approach can be used to show the general circumstances under which different combinations of critical effect sizes and maximum acceptable combinations of and {beta} are attainable for different statistical tests. The optimal sample size estimation approach can require fewer samples than traditional sample size estimation methods when costs of Type I and II errors are assumed to be equal but recommends comparatively more samples for increasingly unequal Type I vs. Type II errors costs. When sampling costs and absolute costs of Type I and II errors are known, optimal sample size estimation can be used to determine the smallest sample size at which the cost of an additional sample outweighs its associated reduction in errors. Optimal sample size estimation constitutes a more flexible and intuitive tool than traditional sample size estimation approaches, given the constraints and unknowns commonly faced by ecologists during study.

ecology↗

bioRxiv2018

Nearly all new protein-coding predictions in the CHESS database are not protein-coding

In a 2018 paper posted to bioRxiv, Pertea et al. presented the CHESS database, a new catalog of human gene annotations that includes 1,178 new protein-coding predictions. These are based on evidence of transcription in human tissues and homology to earlier annotations in human and other mammals. Here, we reanalyze the evidence used by CHESS, and find that nearly all protein-coding predictions are false positives. We find that 86% overlap transposons marked by RepeatMasker that are known to frequently result in false positive protein-coding predictions. More than half are homologous to only nine Alu-derived primate sequences corresponding to an erroneous and previously withdrawn Pfam protein domain. The entire set shows poor evolutionary conservation and PhyloCSF protein-coding evolutionary signatures indistinguishable from noncoding RNAs, indicating lack of protein-coding constraint. Only four predictions are supported by mass spectrometry evidence, and even those matches are inconclusive. Overall, the new protein-coding predictions are unsupported by any credible experimental or evolutionary evidence of function, result primarily from homology to genes incorrectly classified as protein-coding, and are unlikely to encode functional proteins.

genomics↗