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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 Read source abstracts and check manuscript versions; preprints are not peer reviewed.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 91 records · Page 5Linked to original sources

New opabiniid diversifies the weirdest wonders of the euarthropod lower stem group

Once considered weird wonders of the Cambrian, the emblematic Burgess Shale animals Anomalocaris and Opabinia are now recognized as lower stem-group euarthropods. Anomalocaris and its relatives (radiodonts) had a worldwide distribution and survived until at least the Devonian, whereas - despite intense study - Opabinia remains the only formally described opabiniid to date. Here we reinterpret a fossil from the Wheeler Formation of Utah as a new opabiniid, KUMIP 314087. By visualizing the sample of phylogenetic topologies in treespace, our results fortify support for the position of KUMIP 314087 beyond the nodal support traditionally applied. Our phylogenetic evidence expands opabiniids to multiple Cambrian Stages spanning approximately five million years. Our results underscore the power of treespace visualization for resolving imperfectly preserved fossils and expanding the known diversity and spatiotemporal ranges within the euarthropod lower stem group. Additional noteThis work contains a new biological name. New names in preprints are not considered available by the ICZN. To avoid ambiguity, the new biological name is not included in this preprint, and the specimen number (KUMIP 314087) is used as a placeholder. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/434726v1_ufig1.gif" ALT="Figure 1"> View larger version (98K): org.highwire.dtl.DTLVardef@e770aaorg.highwire.dtl.DTLVardef@95bbd3org.highwire.dtl.DTLVardef@5e460eorg.highwire.dtl.DTLVardef@1494152_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOCover image.C_FLOATNO Artistic reconstruction of the new opabiniid from the Wheeler Formation, Utah, USA (Cambrian: Drumian). Artwork by F. Anthony. C_FIG

paleontology↗

Age-related declines in neural selectivity manifest differentially during encoding and recognition

The authors have withdrawn the preprint due to two errors in the analyses: The first error was a failure to account for three dummy volumes (TR = 2s) collected at the beginning of each experimental run. The second error was a coding error related to the definition of the category-selective clusters. Since correcting for these errors drastically altered the results and conclusions of this paper, the authors have withdrawn the preprint and retracted the published paper (https://doi.org/10.1016/j.neurobiolaging.2021.12.001). A report comparing original and corrected results can be found on https://osf.io/7n3mz/. If you have any questions please contact the corresponding author (sander@mpib-berlin.mpg.de).

neuroscience↗

Triangulation reduces the polygon of error for the history of Transeurasian

In a recent study we used an interdisciplinary approach combining linguistics, archaeology and genetics to analyse the Transeurasian languages1. Our analysis concluded that the early dispersals of these languages were driven by agriculture. A preprint published on this server presents objections to the Transeurasian hypothesis and its association with farming dispersals2. However, close inspection of that text reveals numerous misinterpretations and inconsistencies. In the interest of furthering scientific debate over Transeurasian language and population history, we address the critiques, revising datasets and fine-tuning approaches. The linguistic critique questions the quantity and quality of our datasets. Here we show that the number of surviving cognate sets for Transeurasian is in line with that for well-established language families. In addition, we find that Tian et al.s failure to reject a core of regularly corresponding cognates in the basic vocabulary creates ground for a consensus about the genealogical relatability of the Transeurasian languages. The archaeological critique attempts a re-analysis of one Bayesian test using re-scored data only for northern China. Over half of the suggested re-scorings contain inconsistencies and it is not explained why the re-analysis retains the original data for sites outside northern China, comprising almost 60% of the total. More importantly, the sweeping claim that there is no evidence supporting the prehistoric migrations analysed in our study is not backed by any discussion of the archaeological record. With respect to genetics, the preprint claims a re-analysis showing that the data do not conclusively support the farming-driven dispersal of Turkic, Mongolian, and Tungusic, nor the two-wave spread of farming to Korea. In fact, the only genetic re-analysis presented is limited to samples from Korea and Japan and does not contradict our original conservative modelling of Neolithic individuals with Hongshan and our Bronze Age ones with Upper Xiajiadian. In sum, in bringing multiple lines of evidence together through triangulation, we gained a more balanced and richer understanding of Transeurasian dispersals than each discipline could provide individually. Our research doubtless leaves room for improvement but we remain confident that triangulation did not fail, but rather brought us a step closer to understanding the history of the Transeurasian languages.

evolutionary biology↗

Unraveling Genomic Diversity in Pseudomonas aeruginosa Cystic Fibrosis Lung Infection and Its Impact on Antimicrobial Resistance

Pseudomonas aeruginosa is an opportunistic pathogen which causes chronic, drug-resistant lung infections in cystic fibrosis (CF) patients. In this study, we explore the role of genomic diversification and evolutionary trade-offs in antimicrobial resistance (AMR) diversity within P. aeruginosa populations sourced from CF lung infections. We analyzed 300 clinical isolates from four CF patients (75 per patient), and found that genomic diversity is not a consistent indicator of phenotypic AMR diversity. Remarkably, some genetically less diverse populations showed AMR diversity comparable to those with significantly more genetic variation. We also observed that hypermutator strains frequently exhibited increased sensitivity to antimicrobials, contradicting expectations from their treatment histories. Investigating potential evolutionary trade-offs, we found no substantial evidence of collateral sensitivity among aminoglycoside, beta-lactam, or fluoroquinolone antibiotics, nor did we observe trade-offs between AMR and growth in conditions mimicking CF sputum. Our findings suggest that (i) genomic diversity is not a prerequisite for phenotypic AMR diversity; (ii) hypermutator populations may develop increased antimicrobial sensitivity under selection pressure; (iii) collateral sensitivity is not a prominent feature in CF strains, and (iv) resistance to a single antibiotic does not necessarily lead to significant fitness costs. These insights challenge prevailing assumptions about AMR evolution in chronic infections, emphasizing the complexity of bacterial adaptation during infection. ImportanceUpon infection in the cystic fibrosis (CF) lung, Pseudomonas aeruginosa rapidly acquires genetic mutations, especially in genes involved in antimicrobial resistance (AMR), often resulting in diverse, treatment-resistant populations. However, the role of bacterial population diversity within the context of chronic infection is still poorly understood. In this study, we found that hypermutator strains of P. aeruginosa in the CF lung undergoing treatment with tobramycin evolved increased sensitivity to tobramycin relative to non-hypermutators within the same population. This finding suggests that antimicrobial treatment may only exert weak selection pressure on P. aeruginosa populations in the CF lung. We further found no evidence for collateral sensitivity in these clinical populations, suggesting that collateral sensitivity may not be a robust, naturally occurring phenomenon for this microbe. Preprint servers: This manuscript has been submitted as a preprint to bioRxiv

microbiology↗

Biophysics of sodium channels during subthreshold depolarization in vitro and in silico

Voltage-gated sodium channels (VGSC) in the peripheral nervous system shape action potentials (AP) and thereby support the detection of sensory stimuli. Most of the nine mammalian VGSC subtypes are expressed in nociceptors, but predominantly, three are linked to several human pain syndromes: while Nav1.7 is suggested to be a (sub-)threshold channel, Nav1.8 is thought to support the fast AP upstroke. Nav1.9, as it produces large persistent currents, is attributed a role in determining the resting membrane potential. We characterized gating of Nav1.1-Nav1.3 and Nav1.5-Nav1.9 in manual patch clamp with focus on the AP subthreshold depolarization phase. Nav1.9 exhibited the most hyperpolarized activation while its fast inactivation resembled the depolarized inactivation of Nav1.8. For some VGSCs (e.g., Nav1.1 and Nav1.2), a positive correlation between ramp current and window current was detected. Using a modified Hodgkin-Huxley model which accounts for the time needed for inactivation to occur, we used the acquired data to simulate two nociceptive nerve fiber types (an A{delta}-and a mechano-insensitive C-nociceptor) containing VGSC conductances according to published human RNAseq data. Our simulations suggest that Nav1.9 is supporting both the AP upstroke and its shoulder. A reduced threshold for AP generation was induced by enhancing Nav1.7 conductivity or shifting its activation to more hyperpolarized potentials, as observed in Nav1.7-related pain disorders. Here, we provide a comprehensive, comparative functional characterization of VGSCs relevant in nociception and describe their gating with Hodgkin-Huxley-like models, which can serve as a tool to study their specific contributions to AP shape and sodium channel-related diseases. DisclaimerParts of this study were published as a preprint on bioRxiv: Koster, P.A., T. Stiehl, J. Tigerholm, A. Maxion, B. Namer, and A. Lampert. 2023. Biophysics of sodium channels during subthreshold depolarization in vitro and in silico. bioRxiv. doi.org/10.1101/2023.09.03.556095 (Preprint posted September 6, 2023) SummarySubthreshold gating of seven sodium channels (Nav1.1-3, Nav1.5-8) is determined by manual patch clamp and, together with Nav1.9, integrated into a computer model of an A{delta}-and a mechano-insensitive nociceptor (CMi). Simulations reveal contribution of Nav1.9 to the action potential upstroke and shoulder and prove useful for Nav1.7-related disease modelling.

physiology↗

Tartrazine cannot make live tissues transparent

Withdrawal StatementThe authors have withdrawn their manuscript because one of the conclusions was wrong. The authors sincerely apologize to Ou et al. and the research community for the confusion. In this preprint, the authors performed an abdominal skin clearing experiment following the methods section in Ou et al. (ref. 1) and observed only a marginal clearing effect. In this condition (Figure 1), the authors detected tartrazine only in the stratum corneum (SC) of the skin, where only dead cells are present (Figure 1E, F). However, following a more detailed protocol with additional tips kindly provided by Ou et al. (ref. 1), the abdominal skin became more transparent. It seems that mechanical damage to the SC barrier is critical for successful clearing. In this condition, the authors detected strong tartrazine signals under the SC, including the dermis where live cells are located. We are still concerned about the issue of osmolality and toxicity to live cells; cleared cells must be under hypertonic conditions (Figure 3 and 4). However, since Figure 1 (especially Figure 1E, F) no longer stands, and the title can be misinterpreted as if the original results (ref. 1) were irreproducible, the authors believe it is best to withdraw this preprint. 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.

bioengineering↗

Effect of inactivated conditioned media from DENV-2-infected endothelial cells on epithelial cell healing: live cell imaging analysis.

Withdrawal StatementThe authors have withdrawn their manuscript because Several authors have expressed strong opposition to publishing in preprint, as they believe there are still important details, key experiments, and additional tests needed to complete the research. The authors argue that the study is not yet ready for publication as the investigation is still ongoing. Furthermore, some authors state that they did not grant their approval for preprint publication and therefore do not authorize its release at this stage. For these reasons, we kindly ask that our requests be respected. 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. Thank you very much for your understanding and cooperation.

microbiology↗

Failing to account for RNA quantity inflates background and leads to the misleading appearance that PRC2 and GFP bind to RNA in vivo

We recently published biochemical and quantitative evidence that challenges the widespread claims that PRC2 binds directly to many RNAs in vivo. A recent preprint performs a re-analysis of some of our data using a different metric and claims to identify contradictory results - that PRC2 binds to more RNAs than the well-characterized PTBP1 and SAF-A RNA-binding proteins. The preprint also reports other counterintuitive observations, including that PRC2, and all proteins examined, bind to RNAs that do not exist within the same cell and therefore could not interact in vivo nor could they be UV-crosslinked. Because these observations are incongruent with orthogonal, non-PCR based, measurements as well as fundamental RNA biology, we explored why their analysis would lead to these unexpected observations. After carefully examining the methods used and regenerating the reported results, we found a very simple explanation for these discrepancies: the authors effectively ignore the vast majority of RNAs in the sample. Here we show that this failure to properly account for the total RNA in each sample leads to inaccurate estimates of the true proportions of each RNA in the sample and therefore the enrichment calculated. We find that the number of RNA reads discarded is dependent on the RNA binding properties of the protein and therefore dramatically inflates background signals (e.g., RNA detected with GFP) while deflating specific signals (e.g., RNA detected with PTBP1). Importantly, we show that this issue alone explains the discrepancy between their observations and our previously reported results. The fact that PRC2 binding can only be observed when analyzed in this way further reinforces the fundamental point of our original paper: the existing evidence in support of direct PRC2-RNA binding requires critical re-evaluation.

bioinformatics↗

Investing in Open Science: Key Considerations for Funders

The open science movement aims to transform the research landscape by promoting research transparency in order to enable reproducibility and replicability, lower the barriers for collaboration, and reduce unnecessary duplication. Recently, in recognition of the value of open science, funding agencies have begun to mandate open science policies as a condition in grantee awards. However, operationalization and implementation of an open science policy can have unanticipated costs and logistical barriers, which can impact both the funder, as well as the grantee. These factors should be considered when implementing an open science policy. The Aligning Science Across Parkinsons (ASAP) initiative utilizes a comprehensive open science policy, which, in addition to requiring immediate free online access to all publications, also requires all newly-generated datasets, protocols, code, and key lab materials be shared by the time of publication. Moreover, preprints must be posted to a preprint repository by the time of manuscript submission to a journal for review. Here, we outline the potential costs associated with implementing and enforcing this open science policy. We recommend that funders take these considerations into account when investing in open science policies within the biomedical research ecosystem.

scientific communication and education↗

The NIH BRAIN Initiative's Experiment in Team Research

Withdrawal StatementThe authors have withdrawn this manuscript because this manuscript has been merged with another preprint (BIORXIV/2025/635684). 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:10.1101/2025.01.30.635684

neuroscience↗

Production, Purification, and Crystallization of Recombinant Epidermal Growth Factor Receptor Tyrosine Kinase Domain (EGFR-TKD) for Drug Screening Applications

Withdrawal StatementWe request the withdrawal of our preprint (MS ID#: BIORXIV/2025/657332) because the experimental data and analyses presented in the current version are not up to date. Additional experiments and methodological clarifications are required for the accurate interpretation of the results. In its current form, the manuscript may lead to misinterpretation. Therefore, to prevent the dissemination of incomplete or outdated information, we request the withdrawal of the preprint.

biochemistry↗

Model-based EEG phenotyping uncovers distinct neurocomputational mechanisms underlying learning impairments across psychopathologies

BackgroundMajor depressive disorder (MDD), bipolar disorder (BP), and schizophrenia (SCZ) involve learning impairments with poorly understood mechanisms. Understanding both the similarities and differences in these mechanisms is important to guide the development of new, targeted interventions. Methods255 participants diagnosed with MDD (n=54), BP (n=47), SCZ (n=67) or without any diagnoses (CTRL; n=87) performed an associative learning task. Computational modeling quantified the mechanistic interplay between working memory (WM) and reinforcement learning (RL). The latent RL and WM signatures in the EEG dynamics showed shared and distinct neurocognitive mechanisms underlying learning. ResultsAll clinical groups showed learning impairments at the behavioral level. Model-based EEG analyses linked these impairments to distinct patterns in the dynamic interplay between latent RL and WM mechanisms, contrasting with the typical patterns observed in CTRL. SCZ was characterized by reduced neural markers of WM, weakening the cooperative influence of WM onto RL (reduced WM recruitment), and reduced integration of negative feedback. Conversely, MDD was characterized by reduced reciprocal influence of RL onto WM, reducing the tendency to upregulate WM contribution with reward history (impaired WM management). Finally, BP was characterized by deficits in both WM and RL recruitment, along with higher WM decay. ConclusionsBehavioral learning impairments that appear similar across clinical groups can be linked to distinct neurocognitive mechanisms via integrative neurocomputational modeling. Our approach provides insights into the interplay of underlying learning mechanisms and how they manifest differently across psychopathologies. CitationThis manuscript is a preprint version of the later manuscript accepted for publication in Biological Psychiatry: Global Open Science. The content may differ from the final published version following peer review and editorial revisions. Ging-Jehli, N.R., Rac-Lubashevsky, R., Bera, K., Roberts, A., Loder, A., Boudewyn, M.A., Carter, C.S., Erickson, M., Gold, J., Luck, S.J., Ragland, J.D., Yonelinas, A.P., MacDonald III, A.W., Barch, D.M., & Frank, M.J. (2025). Model-based EEG phenotyping uncovers distinct neurocomputational mechanisms underlying learning impairments across psychopathologies. Preprint at bioRxiv.

pathology↗

Hybrid Ornstein-Uhlenbeck-Branching Modeling of Pediatric Leukemia Evolution: A Computational Extension and Cohort-Level Application

Pediatric cancers evolve under developmental constraints that limit mutational diversity yet preserve adaptive potential. A computational extension of the Hybrid Ornstein-Uhlenbeck (OU)-Branching framework was developed to model clonal diversification and phenotypic stabilization in pediatric leukemia. The OU component captures mean-reverting dynamics representing developmental homeostasis, while the branching component introduces stochastic lineage bifurcation and extinction. Using de-identified clinical metadata from Ahlgren et al. (Nature Communications, 2025; 16:8964), the model simulates patient-specific evolutionary trajectories across relapse categories and disease subtypes (B-ALL, T-ALL, MPAL, AML). Simulations reproduce observed clinical trends--rapid relapse and limited diversification in early or refractory KMT2A-r ALL, and slower, therapy-resistant relapses in AML. Group- and patient-level analyses demonstrate how the balance between stabilizing selection ({theta}) and diversification rate ({lambda}) determines clonal persistence and phenotypic drift. This computational implementation provides a quantitative framework for linking developmental constraint, clonal diversity, and therapeutic response in pediatric malignancies and establishes a tractable platform for model-driven hypothesis testing and translational oncology. Statement of Relationship to Prior WorkThis preprint represents a computational and cohort-level extension of the hybrid OU-Branching framework introduced in the authors manuscript currently under review at Frontiers in Oncology ("A hybrid Ornstein-Uhlenbeck-branching framework unifies microbial and pediatric tumor evolution," Manuscript ID 1727973). The Frontiers paper focuses on experimental validation and cross-domain analogies between microbial long-term evolution experiments (LTEE) and pediatric tumor evolution, emphasizing biological interpretation. In contrast, this preprint focuses on clinical modeling, patient specific simulations, and computational methods applied to pediatric KMT2A-rearranged leukemia. No data, text, or figures are duplicated from the in-review article. All code and simulations presented here are novel and will be released upon publication.

cancer biology↗

Exploring the single-cell RNA-seq analysis landscape with the scRNA-tools database

As single-cell RNA-sequencing (scRNA-seq) datasets have become more widespread the number of tools designed to analyse these data has dramatically increased. Navigating the vast sea of tools now available is becoming increasingly challenging for researchers. In order to better facilitate selection of appropriate analysis tools we have created the scRNA-tools database (www.scRNA-tools.org) to catalogue and curate analysis tools as they become available. Our database collects a range of information on each scRNA-seq analysis tool and categorises them according to the analysis tasks they perform. Exploration of this database gives insights into the areas of rapid development of analysis methods for scRNA-seq data. We see that many tools perform tasks specific to scRNA-seq analysis, particularly clustering and ordering of cells. We also find that the scRNA-seq community embraces an open-source approach, with most tools available under open-source licenses and preprints being extensively used as a means to describe methods. The scRNA-tools database provides a valuable resource for researchers embarking on scRNA-seq analysis and records of the growth of the field over time.\n\nAuthor summaryIn recent years single-cell RNA-sequeing technologies have emerged that allow scientists to measure the activity of genes in thousands of individual cells simultaneously. This means we can start to look at what each cell in a sample is doing instead of considering an average across all cells in a sample, as was the case with older technologies. However, while access to this kind of data presents a wealth of opportunities it comes with a new set of challenges. Researchers across the world have developed new methods and software tools to make the most of these datasets but the field is moving at such a rapid pace it is difficult to keep up with what is currently available. To make this easier we have developed the scRNA-tools database and website (www.scRNA-tools.org). Our database catalogues analysis tools, recording the tasks they can be used for, where they can be downloaded from and the publications that describe how they work. By looking at this database we can see that developers have focued on methods specific to single-cell data and that they embrace an open-source approach with permissive licensing, sharing of code and preprint publications.

bioinformatics↗

Conserving unprotected important coastal habitats in the Yellow Sea: shorebird occurrence, distribution and food resources at Lianyungang

The authors have withdrawn their manuscript since this preprint contain errors which have been corrected in the version published in the journal Global Ecology and Conservation (doi: 10.1016/j.gecco.2019.e00724). Therefore, the authors do not wish this preprint to be cited as reference for the project. If you have any questions, please contact the corresponding author.

ecology↗

A systematic review and evaluation of Zika virus forecasting and prediction research during a public health emergency of international concern

INTRODUCTIONEpidemic forecasting and prediction tools have the potential to provide actionable information in the midst of emerging epidemics. While numerous predictive studies were published during the 2016-2017 Zika Virus (ZIKV) pandemic, it remains unknown how timely, reproducible and actionable the information produced by these studies was.\n\nMETHODSTo improve the functional use of mathematical modeling in support of future infectious disease outbreaks, we conducted a systematic review of all ZIKV prediction studies published during the recent ZIKV pandemic using the PRISMA guidelines. Using MEDLINE, EMBASE and grey literature review, we identified studies that forecasted, predicted or simulated ecological or epidemiological phenomenon related to the Zika pandemic that were published as of March 01, 2017. Eligible studies underwent evaluation of objectives, data sources, methods, timeliness, reproducibility, accessibility and clarity by independent reviewers.\n\nRESULTS2034 studies were identified, of which n = 73 met eligibility criteria. Spatial spread, R0 (basic reproductive number) and epidemic dynamics were most commonly predicted, with few studies predicting Guillain-Barre Syndrome burden (4%), sexual transmission risk (4%) and intervention impact (4%). Most studies specifically examined populations in the Americas (52%), with few African-specific studies (4%). Case count (67%), vector (41%) and demographic data (37%) were the most common data sources. Real-time internet data and pathogen genomic information were used in 7% and 0% of studies, respectively, and social science and behavioral data were typically absent in modeling efforts. Deterministic models were favored over stochastic approaches. Forty percent of studies made model data entirely available, 29% provided all relevant model code, 43% presented uncertainty in all predictions and 54% provided sufficient methodological detail allowing complete reproducibility. Fifty-one percent of predictions were published after the epidemic peak in the Americas. While the use of preprints improved the accessibility of ZIKV predictions by a median 119 days sooner than journal publication dates, they were used in only 30% of studies.\n\nCONCLUSIONSMany ZIKV predictions were published during the 2016-2017 pandemic. The accessibility, reproducibility, timeliness, and incorporation of uncertainty in these published predictions varied and indicates that there is substantial room for improvement. To enhance the utility of analytical tools for outbreak response, it is essential to improve the sharing of model data, code, and preprints for future outbreaks, epidemics and pandemics.\n\nAuthor summaryResearchers published many studies which sought to predict and forecast important features of Zika virus (ZIKV) infections and their spread during the 2016-2017 ZIKV pandemic. We conducted a comprehensive review of such ZIKV prediction studies and evaluated their aims, the data sources they used, which methods were used, how timely they were published, and whether they provided sufficient information to be used or reproduced by others. Of the 73 studies evaluated, we found that the accessibility, reproducibility, timeliness, and incorporation of uncertainty in these published predictions varied and indicates that there is substantial room for improvement. We identified that the release of study findings before formal journal publication ( pre-prints) increased the timeliness of Zika prediction studies, but note they were infrequently used during this public health emergency. Addressing these areas can improve our understanding of Zika and other outbreaks and ensure that forecasts can inform preparedness and response to future outbreaks, epidemics and pandemics.

epidemiology↗

Effect of Testosterone on Antler Growth in Male Sambar Deer (Rusaunicolor unicolor) in Horton Plains National Park, Sri Lanka.

The authors have withdrawn this manuscript because it underwent a major revision since it was last posted on bioRxiv. However, the preprint number 740936 underwent a major revision since it was last posted on bioRxiv and a link to the published article in the journal BioMed Research International with a revised title as “The antler cycle and fecal testosterone of male sambar deer Rusa unicolor unicolor at the Horton Plains National Park in Sri Lanka” is forthcoming. The peer review process resulted in changes to the title as well as the methods, results and conclusions sections of the preprint. 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.Competing Interest StatementWithdrawn

zoology↗