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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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At least 109 records · Page 6Linked to original sources

Cumulative geomagnetic disturbances modulate global photosystem stoichiometry through temperature-dependent gating

The authors have withdrawn their manuscript because a subsequent audit identified implementation errors in the analytical pipeline used for the preprint, affecting environmental-data ingestion and temporal feature construction, spatial grid registration, rank handling, and the treatment of temporal autocorrelation in pooled space-time analyses. These issues affect several numerical results and inferential statements in the posted version. A substantially revised analysis, developed from a separate analytical branch, was subsequently peer reviewed and published in Biology (2026), 15, 1415 (DOI: 10.3390/biology15161415), and represents the final analysis of the project. Because revisions can no longer be posted after journal publication, the authors are withdrawing the preprint rather than leaving the uncorrected version as the current record. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

biophysics↗

Cross-Species Adaptation of RETFound for Rodent OCT Age Estimation Reveals Strong CNN Baselines in Data-Scarce Space Biology

Space-biology imaging studies are often constrained by severe data scarcity, limiting the development of robust machine-learning biomarkers. Rodent spaceflight and space-analog datasets provide an important preclinical setting for testing transfer-learning strategies, but the extent to which human retinal foundation models can generalize to rodent optical coherence tomography (OCT) remains unclear. Here, we benchmark cross-species adaptation of RETFound, a human retinal Vision Transformer pretrained on 1.6 million retinal images, for chronological age prediction from Brown Norway rat OCT B-scans in the NASA Open Science Data Repository dataset OSD-679. We adapted RETFound using Low-Rank Adaptation (LoRA) and evaluated performance on control animals under matched 3-fold rat-level cross-validation. We compared RETFound+LoRA with a strong ImageNet-pretrained Xception baseline under matched protocols and included a scratch/random ViT as a supplementary negative-control architecture check. Metrics included mean absolute error (MAE), R2, and inter-eye mean absolute difference (MAD). RETFound+LoRA achieved MAE = 26.20 {+/-} 5.03 days with R2 = 0.744 {+/-} 0.049. However, Xception performed better in the primary benchmark (MAE = 19.01 {+/-} 7.67 days, R2 = 0.853 {+/-} 0.082), and the matched-fold comparison favored Xception, although this result should be interpreted cautiously given the small number of folds. Inter-eye consistency was maintained across the matched control evaluation, and saliency maps localized model attention to anatomically plausible inner retinal regions. Together, these results show that human retinal foundation models can transfer to rodent OCT in a scientifically useful way, but also that strong CNN baselines may outperform transformer-based models in small-sample cross-species settings. This preprint provides a reproducible benchmark and baseline framework for future retinal biomarker development in space biology. Significance StatementSpace-biology imaging studies are intrinsically data-limited. This preprint provides a reproducible cross-species benchmark for adapting Earth-trained retinal models to rodent OCT under small-sample conditions, highlights the value of strong CNN baselines, and offers a reusable starting point for future retinal biomarker development in space-relevant datasets.

bioinformatics↗

BIOTIA-DX RESISTANCE Achieved the Best Antimicrobial Resistance Phenotype Prediction Accuracy at CAMDA 2026

We present BIOTIA-DX RESISTANCE (BDXR), our submission to the CAMDA 2026 AMR Challenge. This work extends our CAMDA 2025 submission [1] to a new set of six species-drug pairs and adds k-mer-based feature engineering (both targeted and whole-genome) for pairs where the 2025 gene-presence base model underperforms. BDXR achieved a mean accuracy of 86.1% across the six pairs on the CAMDA 2026 test set, ranking first on four pairs, tied for first on Streptococcus pneumoniae (penicillin), and second on Campylobacter jejuni (nalidixic acid); per-pair test accuracy ranged from 69.9% (C. jejuni, nalidixic acid) to 98.8% (S. pneumoniae, penicillin). We refer the reader to our 2025 preprint [1] for the underlying workflow, dataset curation, and clinical motivation; this preprint focuses on the results and methodological changes that are new in 2026.

microbiology↗

A Temporal Atlas of the Nuclear Androgen Receptor Proximal Interactome

The authors have withdrawn this manuscript because this manuscript has been merged with another preprint (BIORXIV/2026/742469). Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author. The merged preprint can be found at doi: 10.64898/2026.08.03.742469

systems biology↗

Using 2k + 2 bubble searches to find SNPs in k-mer graphs

This preprint is now available in published form as: Using 2k + 2 bubble searches to find SNPs in k-mer graphs, Reda Younsi; Dan MacLean, Bioinformatics 2014; doi: 10.1093/bioinformatics/btu706\n\nSingle Nucleotide Polymorphism (SNP) discovery is an important preliminary for understanding genetic variation. With current sequencing methods we can sample genomes comprehensively. SNPs are found by aligning sequence reads against longer assembled references. De Bruijn graphs are efficient data structures that can deal with the vast amount of data from modern technologies. Recent work has shown that the topology of these graphs captures enough information to allow the detection and characterisation of genetic variants, offering an alternative to alignment-based methods. Such methods rely on depth-first walks of the graph to identify closing bifurcations. These methods are conservative or generate many false-positive results, particularly when traversing highly inter-connected (complex) regions of the graph or in regions of very high coverage.We devised an algorithm that calls SNPs in converted De Bruijn graphs by enumerating 2k + 2 cycles. We evaluated the accuracy of predicted SNPs by comparison with SNP lists from alignment based methods. We tested accuracy of the SNP calling using sequence data from sixteen ecotypes of Arabidopsis thaliana and found that accuracy was high. We found that SNP calling was even across the genome and genomic feature types. Using sequence based attributes of the graph to train a decision tree allowed us to increase accuracy of SNP calls further.Together these results indicate that our algorithm is capable of finding SNPs accurately in complex sub-graphs and potentially comprehensively from whole genome graphs.The source code for a C++ implementation of our algorithm is available under the GNU Public Licence v3 at:https://github.com/redayounsi/2kplus2

Bioinformatics↗

DoOR 2.0 - Comprehensive Mapping of Drosophila melanogaster Odorant Responses

Odors elicit complex patterns of activated olfactory sensory neurons. Knowing the complete olfactome, i.e. responses in all sensory neurons for all odorants, is desirable to understand olfactory coding. The DoOR project combines all available Drosophila odorant response data into a single consensus response matrix. Since its first release many studies were published: receptors were deorphanized and several response profiles were expanded. In this study, we add to the odor-response profiles for four odorant receptors (Or10a, Or42b, Or47b, Or56a). We deorphanize Or69a, showing a broad response spectrum with the best ligands including 3-hydroxyhexanoate, alpha-terpineol, 3-octanol and linalool. We include these datasets into DoOR, and provide a comprehensive update of both code and data. The DoOR project has a web interface for quick queries (http://neuro.uni.kn/DoOR), and a downloadable, open source toolbox written in R, including all processed and original datasets. DoOR now gives reliable odorant-responses for nearly all Drosophila olfactory responding units, listing 693 odorants, for a total of 7381 data points.\n\nAt the time of uploading this preprint, a preview of the DoOR 2.0 webpage is available at: http://neuro.uni.kn/DoOR/2.0

Neuroscience↗

Low-temperature-specific effects of PHYTOCHROME C on the circadian clock in Arabidopsis suggest that PHYC underlies natural variation in biological timing

The circadian clock is a fundamental feature of gene regulation and cell physiology in eukaryotes and some prokaryotes, and an exemplar gene regulatory network in Systems Biology. The circadian system in Arabidopsis thaliana is complex in part due to its photo-transduction pathways. Analysis of natural genetic variation between Arabidopsis accessions Cape Verde Islands (Cvi-0) and Landsberg erecta (Ler) identified a major, temperature-specific Quantitative Trait Locus (QTL) on chromosome V that altered the circadian period of leaf movement (Edwards et al., Genetics, 2005). We tested Near-Isogenic Lines (NILs) to confirm that Ler alleles at this PerCv5c QTL lengthened the circadian period at 12{degrees}C, with little effect at higher temperatures. The PHYTOCHROME C gene lies within the QTL interval, and contains multiple sequence variants. Plants carrying either a T-DNA-insertion into PHYC or a deletion of PHYC also lengthened circadian period under white light, except at 27{degrees}C. phyB and phyABE mutants lengthened period only at 12{degrees}C. These results extend recent data showing PhyC effects in red light, confirming the number of photoreceptor proteins implicated in the plant circadian system at eleven. The connection between light input mechanisms and temperature effects on the clock is reinforced. Natural genetic variation within PHYC is likely to underlie the PerCv5c QTL. Our results suggest that functional variation within the PHYC-Ler haplotype group might contribute to the evolution of the circadian system and possibly to clock-related phenotypes such as flowering time. These results have previously passed peer-review, so we provide them in this citable preprint.

Genetics↗

No ′small genome attraction′ artifact: A response to Harish et al. ′Did viruses evolve as a distinct supergroup from common ancestors of cells?′

In a recent eLetter and associated preprint, Harish, Abroi, Gough and Kurland criticized our structural phylogenomic methods, which support the early cellular origin of viruses. Their claims include the argument that the rooting of our trees is artifactual and distorted by small genome (proteome) size. Here we uncover their aprioristic reasoning, which mingles with misunderstandings and misinterpretations of cladistic methodology. To demonstrate, we labeled the phylogenetic positions of the smallest proteomes in our phylogenetic trees and confirm that the smallest genomes were neither attracted towards the root nor caused any distortions in the four-supergroup tree of life. Their results therefore stem from confusing outgroups with ancestors and handpicking problematic taxa to distort tree reconstruction. In doing so, they ignored the details of our rooting method, taxa sampling rationale, the plethora of evidence given in our study supporting the ancient origin of the viral supergroup and also recent literature on viral evolution. Indeed, our tree of life uncovered many viral monophyletic groups consistent with ICTV classifications and showed remarkable evolutionary tracings of virion morphotypes onto a revealing tree topology.

Evolutionary Biology↗

Structure, interaction and post-translational modification study of arsenic reduction system in Bifidobacterium longum

Microbial metabolism contributes to degradation of organoarsenicals, where arsenic reductases (glutaredoxins) play pivotal role in bacterial resistance to arsenic. Ars operon studies have revealed reduction of arsenate As(V) to arsenite As(III) by respiratory-chain-linked reductase enzyme complexes. Although structure of some bacterial arsenate reductases has been solved but not attempted for Bifidobacterium longum DJO10A colonizing the human gastrointestinal tract. Here it has been endeavoured to analyze and understand the structure, properties, interaction, evolution and action mechanism of this enzyme (arsC1) and its accessory interactors (arsB1, arsB2 and arsR). A systematic bioinformatic based analysis was carried out using a battery of tools and web servers for this purpose. Arsenic resistance gene cluster of gram-positive Bifidobacterium obtained from STRING database illustrated contiguous arsC and arsB genes and absence of arsA gene. ArsC1 was determined to be a cytoplasmic small-molecular-mass protein (~15 kDa) related to a class of tyrosine phosphatases mediating the reduction of As(V) to As(III). ArsC1 was found to be involved in dephosphorylation of arsR, arsB1 and arsB2, indicating its role in post translational modification (PTM) of interacting proteins. 3D structure analysis revealed that it was composed of 1 sheet,1 beta alpha beta unit, 4 strands, 5 helices, 3 helix-helix interacs, 13 beta turns and 1 gamma turn. All proteins in the cluster exhibited hydrophobic interactions. Explicit protein-protein hydrogen, ionic, aromatic and cation-pi interactions in arsenate reducing operon of Bifidobacterium longum DJO10A further aided structural understanding of arsenate reduction process.\n\nNoteThis research was carried out in 2015. Availability of new information or changes in the algorithm behind software/database used for text mining interaction analysis in the meantime might impact some of the analyzed values. The preprint version may contain grammatical and proofreading mistakes. Errors and omissions excepted.

Bioinformatics↗

Sequence based prediction of novel domains in the cellulosome of Ruminiclostridium thermocellum

Ruminiclostridium thermocellum strain ATCC 27405 is valuable with reference to the next generation biofuel production being a degrader of crystalline cellulose. The completion of its genome sequence has revealed that this organism carries 3,376 genes with more than hundred genes encoding for enzymes involved in cellulysis. Novel protein domain discovery in the cellulose degrading enzyme complex of this strain has been attempted to understand this organism at molecular level. Streamlined automated methods were employed to generate possibly unreported or new domains. A set of 12 novel Pfam-B domains was developed after detailed analysis. This finding will enhance our understanding of this bacterium and its molecular processes involved in the degradation of cellulose. This approach of in silico analysis prior to experimentation facilitates in lab study. Previously uncorrelated data has been utilized for rapid generation of new biological information in this study.\n\nNoteThis research was conducted in 2014 for Clostridium thermocellum ATCC 27405. The bacterium was later reannotated as Ruminiclostridium thermocellum. See NCBI nonredundant RefSeq protein annotation details at http://www.ncbi.nlm.nih.gov/refseq/about/prokaryotes/reannotation/. The study utilizes Pfam-B database, which was discontinued with effect from release 28.0 (5/2015). Availability of new information, reannotation/modification in accession numbers might impact some of the analyzed values although effort has been made to provide latest accession numbers and reference strain parameters. The preprint version may contain grammatical and proofreading mistakes. Errors and omissions excepted.

Microbiology↗

Maintenance of Polymorphism in Spatially Heterogeneous Environments: An Experimental Test of Hard and Soft Selection

This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (http://dx.doi.org/10.24072/pci.evolbiol.100020). Predicting and managing contemporary adaption requires a proper understanding of the determinants of genetic variation. Spatial heterogeneity of the environment may stably maintain polymorphism when habitat contribution to the next generation can be considered independent of the degree of adaptation of local populations within habitats (i.e., under soft selection). In contrast, when habitats contribute proportionally to the mean fitness of the populations they host (hard selection), polymorphism is not expected to be maintained by selection. Although mathematically established decades ago, this prediction had never been properly explored. Here we provide an experimental test in which polymorphic populations of Escherichia coli growing in heterogeneous habitats were exposed to hard and soft selection regimes. As predicted by theory, polymorphism was longer preserved under soft selection. Complementary tests established that soft selection slowed down fixation processes and could even protect polymorphism on the long term by providing a systematic advantage to rare genotypes.

evolutionary biology↗

Preserving microsatellites? Conservation genetics of the giant Galapagos tortoise.

This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (http://dx.doi.org/10.24072/pci.evolbiol.100031).\n\nConservation policy in the giant Galapagos tortoise, an iconic endangered animal, has been assisted by genetic markers for [~]15 years: a dozen loci have been used to delineate thirteen (sub)species, between which hybridization is prevented. Here, comparative reanalysis of a previously published NGS data set reveals a conflict with traditional markers. Genetic diversity and population substructure in the giant Galapagos tortoise are found to be particularly low, questioning the genetic relevance of current conservation practices. Further examination of giant Galapagos tortoise population genomics is critically needed.

evolutionary biology↗

Can Ebola Virus evolve to be less virulent in humans?

This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology ( ). Understanding Ebola Virus (EBOV) virulence evolution is not only timely but also raises specific questions because it causes one of the most virulent human infections and it is capable of transmission after the death of its host. Using a compartmental epidemiological model that captures three transmission routes (by regular contact, via dead bodies and by sexual contact), we infer the evolutionary dynamics of case fatality ratio (CFR) on the scale of an outbreak and on the long term. Our major finding is that the viruss specific life cycle imposes selection for high levels of virulence and that this pattern is robust to parameter variations in biological ranges. In addition to shedding a new light on the ultimate causes of EBOVs high virulence, these results generate testable predictions and contribute to informing public health policies. In particular, burial management stands out as the most appropriate intervention since it decreases the R0 of the epidemics, while imposing selection for less virulent strains.\n\nImpact SummaryThe severe haemorrhagic fever caused by Ebola Virus (EBOV) usually kills more than one infected individual out of two in the absence of treatment, which makes this pathogen one of the most virulent known to humans. The recent outbreak in West Africa (2013-2016) revealed that the virus is able to spread and persist for months across countries. It is often thought that virulence could be due to the fact that the virus is adapted to its reservoir host. Given that microbes evolve rapidly, it is important to determine whether EBOV virulence is likely to decrease as the virus adapts to its human host. To address this problem, we developed a novel mathematical model tailored to EBOVs life cycle, notably by capturing its three main transmission routes (by regular contact, sexual contact and via dead bodies). We investigated the evolutionary trends of EBOVs virulence on different time scales (outbreak initiation, short term and long term). Our results reveal that the virulence of EBOV might not be due to the maladaptation of the virus, but could rather originate from its unique life cycle. These results are robust to the parameter values chosen. From a public health perspective, burial management stands out as the main leverage to fight the virulence of EBOV, both on the short and long terms.

evolutionary biology↗

Despite reproductive interference, the net outcome of reproductive interactions among spider mite species is not necessarily costly

This preprint has been reviewed and recommended by Peer Community in Evolutionary Biology (http://dx.doi.org/10.24072/pci.evolbiol.100025). Reproductive interference is considered a strong ecological force, potentially leading to species exclusion. This supposes that the net effect of reproductive interactions is strongly negative for one of the species involved. Testing this requires a comprehensive analysis of interspecific reproductive interactions, accounting for the order and timing of mating events, and for their effects on either fertility or fecundity. To this aim, we measured reproductive interactions between a focal species, Tetranychus urticae, and an invasive (T.evansi) and a resident (T. ludeni) species, varying the mating sequence and interval, and measuring the effect of such crosses on fecundity and offspring sex ratio (a measure of fertility, as these species are haplodiploid). We found that mating with heterospecifics affected fecundity and sex ratio negatively, but also positively, depending on the species involved, and on the order and timing of mating events. Overall, the net effect of reproductive interactions was weak despite strong effects of particular events. In natural situations, the outcome of reproductive interactions will thus hinge upon the frequency of each event.

ecology↗

Negative frequency-dependent selection is frequently confounding

This preprint has been reviewed and recommended by Peer Community in Evolutionary Biology (http://dx.doi.org/10.24072/pci.evolbiol.100024). The existence of persistent genetic variation within natural populations presents an evolutionary problem as natural selection and genetic drift tend to erode genetic diversity. Models of balancing selection were developed to account for the high and sometimes extreme levels of polymorphism found in many natural populations. Negative frequency-dependent selection may be the most powerful selective force maintaining balanced natural polymorphisms but it is also commonly misinterpreted. The aim of this review is to clarify the processes underlying negative frequency-dependent selection, describe classes of natural polymorphisms that can and cannot result from these processes, and discuss observational and experimental data that can aid in accurately identifying the processes that generated or are maintain diversity in nature. Finally, I consider the importance of accurately describing the processes affecting genetic diversity within populations as it relates to research progress.

evolutionary biology↗

Identifying drivers of parallel evolution: A regression model approach

This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (http://dx.doi.org/10.24072/pci.evolbiol.100045). Parallel evolution, defined as identical changes arising in independent populations, is often attributed to similar selective pressures favoring the fixation of identical genetic changes. However, some level of parallel evolution is also expected if mutation rates are heterogeneous across regions of the genome. Theory suggests that mutation and selection can have equal impacts on patterns of parallel evolution, however empirical studies have yet to jointly quantify the importance of these two processes. Here, we introduce several statistical models to examine the contributions of mutation and selection heterogeneity to shaping parallel evolutionary changes at the gene-level. Using this framework we analyze published data from forty experimentally evolved Saccharomyces cerevisiae populations. We can partition the effects of a number of genomic variables into those affecting patterns of parallel evolution via effects on the rate of arising mutations, and those affecting the retention versus loss of the arising mutations (i.e. selection). Our results suggest that gene-to-gene heterogeneity in both mutation and selection, associated with gene length, recombination rate, and number of protein domains drive parallel evolution at both synonymous and nonsynonymous sites. While there are still a number of parallel changes that are not well described, we show that allowing for heterogeneous rates of mutation and selection can provide improved predictions of the prevalence and degree of parallel evolution.\n\nData archival locationDryad, doi to be included later

evolutionary biology↗

Selection On Morphological Traits And Fluctuating Asymmetry By A Fungal Parasite In The Yellow Dung Fly

A Preprint reviewed and recommended by Peer Community Evolutionary Biology: http://dx.doi.org/10.24072/pci.evolbiol.100027\n\nEvidence for selective disadvantages of large body size remains scarce in general. Previous phenomenological studies of the yellow dung fly Scathophaga stercoraria have demonstrated strong positive sexual and fecundity selection on male and female size. Nevertheless, the body size of flies from a Swiss study population has declined by almost 10% from 1993 to 2009. Given substantial heritability of body size, this negative evolutionary response of an evidently positively selected trait suggests important selective factors being missed (e.g. size-selective predation or parasitism). A periodic epidemic outbreak of the fungus Entomophthora scatophagae allowedassessment of selection exerted by this parasite fatal to adult flies. Fungal infection varied over the season from ca. 50% in the cooler and more humid spring and autumn to almost 0% in summer. The probability of dying from fungal infection increased with adult body size. All infected females died before laying eggs, so there was no fungus impact on female fecundity beyond its impact on mortality. Large males showed the typical mating advantage in the field, but this pattern of positive sexual selection was nullified by fungal infection. Mean fluctuating asymmetry of paired appendages (legs, wings) did not affect the viability, fecundity or mating success of yellow dung flies in the field. This study demonstrates rare parasite-mediated disadvantages of large adult body size in the field. Reduced ability to combat parasites such as Entomophthora may be an immunity cost of large size in dung flies, although the hypothesized trade-off between fluctuating asymmetry, a presumed indicator of developmental instability and environmental stress, and immunocompetence was not found here.

evolutionary biology↗

Reconstruction of body mass evolution in the Cetartiodactyla and mammals using phylogenomic data.

This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (http://dx.doi.org/10.24072/pci.evolbiol.100042).\n\nReconstructing ancestral characters on a phylogeny is an arduous task because the observed states at the tips of the tree correspond to a single realization of the underlying evolutionary process. Recently, it was proposed that ancestral traits can be indirectly estimated with the help of molecular data, based on the fact that life history traits influence substitution rates. Here we challenge these new approaches in the Cetartiodactyla, a clade of large mammals which, according to paleontology, derive from small ancestors. Analysing transcriptome data in 41 species, of which 22 were newly sequenced, we provide a dated phylogeny of the Cetartiodactyla and report a significant effect of body mass on the overall substitution rate, the synonymous vs. non-synonymous substitution rate and the dynamics of GC-content. Our molecular comparative analysis points toward relatively small Cetartiodactyla ancestors, in agreement with the fossil record, even though our data set almost exclusively consists of large species. This analysis demonstrates the potential of phylogenomic methods for ancestral trait reconstruction and gives credit to recent suggestions that the ancestor to placental mammals was a relatively large and long-lived animal.

evolutionary biology↗