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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 Read source abstracts and check manuscript versions; preprints are not peer reviewed.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 271 records · Page 15Linked to original sources
bioRxiv2018

Increased cognitive complexity reveals abnormal brain network activity in individuals with corpus callosum dysgenesis

Cognitive reasoning is thought to require functional interactions between whole-brain networks. Such networks rely on both cerebral hemispheres, with the corpus callosum providing cross-hemispheric communication. Here we used high-field functional magnetic resonance imaging (7T fMRI), a well validated cognitive task, and brain network analyses to investigate the functional networks underlying cognitive reasoning in individuals with corpus callosum dysgenesis (CCD), an anatomical abnormality that affects the corpus callosum. Participants with CCD were asked to solve cognitive reasoning problems while their brain activity was measured using fMRI. The complexity of these problems was parametrically varied by changing the complexity of relations that needed to be established between shapes within each problem matrix. Behaviorally, participants showed a typical reduction in task performance as problem complexity increased. Task-evoked neural activity was observed in brain regions known to constitute two key cognitive control systems: the fronto-parietal and cingulo-opercular networks. Under low complexity demands, network topology and the patterns of local neural activity in the CCD group closely resembled those observed in neurotypical controls. By contrast, when asked to solve more complex problems, participants with CCD showed a reduction in neural activity and connectivity within the fronto-parietal network. These complexity-induced, as opposed to resting-state, differences in functional network activity help resolve the apparent paradox between preserved network architecture found at rest in CCD individuals, and the heterogeneous deficits they display in response to cognitive task demands [preprint: https://doi.org/10.1101/312629].

neuroscience↗
bioRxiv2018

Internal noise in contrast discrimination propagates forwards from early visual cortex

Human contrast discrimination performance is limited by transduction nonlinearities and variability of the neural representation (noise). Whereas the nonlinearities have been well-characterised, there is less agreement about the specifics of internal noise. Psychophysical models assume that it impacts late in sensory processing, whereas neuroimaging and intracranial electrophysiology studies suggest that the noise is much earlier. We investigated whether perceptually-relevant internal noise arises in early visual areas or later decision making areas. We recorded EEG and MEG during a two-interval-forced-choice contrast discrimination task and used multivariate pattern analysis to decode target/non-target and selected/non-selected intervals from evoked responses. We found that perceptual decisions could be decoded from both EEG and MEG signals, even when the stimuli in both intervals were physically identical. Above-chance decision classification started <100ms after stimulus onset, suggesting that neural noise affects sensory signals early in the visual pathway. Classification accuracy increased over time, peaking at >500ms. Applying multivariate analysis to separate anatomically-defined brain regions in MEG source space, we found that occipital regions were informative early on but then information spreads forwards across parietal and frontal regions. This is consistent with neural noise affecting sensory processing at multiple stages of perceptual decision making. We suggest how early sensory noise might be resolved with Birdsalls linearisation, in which a dominant noise source obscures subsequent nonlinearities, to allow the visual system to preserve the wide dynamic range of early areas whilst still benefitting from contrast-invariance at later stages. A preprint of this work is available at: http://dx.doi.org/10.1101/364612

neuroscience↗
bioRxiv2018

Mutational signature analysis of Asian OSCCs reveals novel mutational signature with exceptional sequence context specificity

Mutational signatures can reveal the history of mutagenic processes that cells were exposed to prior to and during tumourigenesis. We expect that as-yet-undiscovered mutational processes will shed further light on mutagenesis leading to carcinogenesis. With this in mind, we analyzed the mutational spectra of 36 Asian oral squamous cell carcinomas. The mutational spectra of two samples from patients who presented with oral bacterial infections, showed novel mutational signatures. One of these novel signatures, SBS_AnT, is characterized by a preponderance of thymine mutations, strong transcriptional strand bias, and striking enrichment for adenines in the 4 base pairs 5 of mutation sites. Examination of publicly available sequencing data revealed SBS_AnT in 25 tumours from several mucosal tissue types, all of which harbour human symbionts or are adjacent to tissues that harbour symbionts. Data in a preprint released while this manuscript was in revision strongly suggest that the bacterial compound colibactin causes SBS_AnT.

genomics↗
bioRxiv2018

Genome-wide repressive capacity of promoter DNA methylation is revealed through epigenomic manipulation

The scientific community is increasingly embracing open science. This growing commitment to open science should be applauded and encouraged, especially when it occurs voluntarily and prior to peer review. Thanks to other researchers dedication to open science, we have had the privilege of conducting a reanalysis of a landmark experiment published as a preprint with data made available in a public repository. The study in question found that promoter DNA methylation is frequently insufficient to induce transcriptional repression, which appears to contradict a large body of observational studies showing a strong association between DNA methylation and gene expression. This study was the first to evaluate whether forcibly methylating thousands of DNA promoter regions is sufficient to suppress gene expression. The authors data analysis did not find a strong relationship between promoter methylation and transcriptional repression. However, their analyses did not make full use of statistical inference and applied a normalization technique that removes global differences that are representative of the actual biological system. Here we reanalyze the data with an approach that includes statistical inference of differentially methylated regions, as well as a normalization technique that accounts for global expression differences. We find that forced DNA methylation of thousands of promoters overwhelmingly represses gene expression. In addition, we show that complementary epigenetic marks of active transcription are reduced as a result of DNA methylation. Finally, by studying whether these associations are sensitive to the CG density of promoters, we find no substantial differences in the association between promoters with and without a CG island. The code needed to reproduce are analysis is included in the public GitHub repository github.com/kdkorthauer/repressivecapacity.

genomics↗
bioRxiv2018

Motor Learning Without Moving: Proprioceptive and Predictive Hand Localization After Passive Visuoproprioceptive Discrepancy Training

An accurate estimate of limb position is necessary for movement planning, before and after motor learning. Where we localize our unseen hand after a reach depends on felt hand position, or proprioception, but in studies and theories on motor adaptation this is quite often neglected in favour of predicted sensory consequences based on efference copies of motor commands. Both sources of information should contribute, so here we set out to further investigate how much of hand localization depends on proprioception and how much on predicted sensory consequences. We use a training paradigm combining robot controlled hand movements with rotated visual feedback that eliminates the possibility to update predicted sensory consequences ( exposure training), but still recalibrates proprioception, as well as a classic training paradigm with self-generated movements in another set of participants. After each kind of training we measure participants hand location estimates based on both efference-based predictions and afferent proprioceptive signals with self-generated hand movements ( active localization) as well as based on proprioception only with robot-generated movements ( passive localization). In the exposure training group, we find indistinguishable shifts in passive and active hand localization, but after classic training, active localization shifts more than passive, indicating a contribution from updated predicted sensory consequences. Both changes in open-loop reaches and hand localization are only slightly smaller after exposure training as compared to after classic training, confirming that proprioception plays a large role in estimating limb position and in planning movements, even after adaptation. (data: https://doi.org/10.17605/osf.io/zfdth, preprint: https://doi.org/10.1101/384941)

neuroscience↗
bioRxiv2018

Parameter tuning is a key part of dimensionality reduction via deep variational autoencoders for single cell RNA transcriptomics

Single-cell RNA sequencing (scRNA-seq) is a powerful tool to profile the transcriptomes of a large number of individual cells at a high resolution. These data usually contain measurements of gene expression for many genes in thousands or tens of thousands of cells, though some datasets now reach the million-cell mark. Projecting high-dimensional scRNA-seq data into a low dimensional space aids downstream analysis and data visualization. Many recent preprints accomplish this using variational autoencoders (VAE), generative models that learn underlying structure of data by compress it into a constrained, low dimensional space. The low dimensional spaces generated by VAEs have revealed complex patterns and novel biological signals from large-scale gene expression data and drug response predictions. Here, we evaluate a simple VAE approach for gene expression data, Tybalt, by training and measuring its performance on sets of simulated scRNA-seq data. We find a number of counter-intuitive performance features: i.e., deeper neural networks can struggle when datasets contain more observations under some parameter configurations. We show that these methods are highly sensitive to parameter tuning: when tuned, the performance of the Tybalt model, which was not optimized for scRNA-seq data, outperforms other popular dimension reduction approaches - PCA, ZIFA, UMAP and t-SNE. On the other hand, without tuning performance can also be remarkably poor on the same data. Our results should discourage authors and reviewers from relying on self-reported performance comparisons to evaluate the relative value of contributions in this area at this time. Instead, we recommend that attempts to compare or benchmark autoencoder methods for scRNA-seq data be performed by disinterested third parties or by methods developers only on unseen benchmark data that are provided to all participants simultaneously because the potential for performance differences due to unequal parameter tuning is so high.

bioinformatics↗
bioRxiv2018

Conditional approach as cooperation in predator inspection: a role for serotonin?

In guppies (Poecilia reticulata), a small number of individuals break away from a shoal and approach a potential predator, a behavior termed "predator inspection". These animals often employ a "conditional approach" strategy, in which an individual approaches the predator in the first move and subsequently approaches it only if a second individual swims even with it during inspection. This strategy is analogous to the "tit-for-tat" strategy of the Prisoners Dilemma, suggesting that it could be used to study cooperation. Serotonin is thought to mediate cooperative behavior in other fish species. Exposure to the animated image of a predator in a tank that contained a parallel mirror - mimicking an equally cooperating conspecific - promoted inspection and decreased refuge use, but increased freezing, suggesting that conditional approach is also associated with fear. To understand whether serotonin participates in conditional approach in guppies, we treated animals with either vehicle (Cortlands salt solution), fluoxetine (2.5 mg/kg) or metergoline (1 mg/kg), and tested then in a predator inspection paradigm. Fluoxetine increased the time the animal spent inspecting the predator image, while metergoline decreased it. Fluoxetine also decreased time spent avoiding the predator and increased freezing, while metergoline decreased freezing. These results suggest that phasic increases in serotonin levels promote conditional approach, suggesting a role for this neurotransmitter in cooperation. Preprint: https://doi.org/10.1101/436345; Data and scripts: https://github.com/lanec-unifesspa/TFT

animal behavior and cognition↗
bioRxiv2019

Hundreds of yeast mRNAs form a separately addressable, translation elongation-controlled regulon

In addition to the widespread and well documented control of protein synthesis by translation initiation, recent evidence suggests that translation elongation can also control protein synthesis rates. One of the proposed mechanisms leading to elongation control is the interference of slow ribosome movement around the start codon with efficient translation initiation. Here we estimate the frequency with which this mode of control occurs in bakers yeast growing in rich medium. Genome-wide data reveal that transcripts from around 20% of yeast genes show evidence of queueing ribosomes, which may be indicative of translation elongation control. Moreover, this subset of transcripts is sensitive to distinct regulatory signals compared to initiation-controlled mRNAs, and such distinct regulation occurs for example during the response to osmotic stress. Notethe previous version 2 of this preprint contained a Decision-Tree based analysis where we attempted to relate mRNA features to the presence or absence of queueing ribosome peaks. Since releasing that version, we performed additional controls for this analysis which strongly sugest that its results are random and should be ignored. Specifically, both the overall predictability and the importance of individual features is very similar for a real dataset where genes are labelled as containing a second SSU peak or not, and for a simulated control dataset containing an equal proportion of randomly labelled genes. We have removed this figure from the current version. The analysis together with the additional control remains accessible on the accompanying Github repository (github.com/tobiasvonderhaar/ribosomespeedcontrol) in the file "Figure 3 Obsolete (Classification).ipynb".

molecular biology↗
bioRxiv2019

AMMISOFT for AMMI Analysis with Best Practices

The Additive Main effects and Multiplicative Interaction (AMMI) model has been used extensively for analysis of multi-environment yield trials for two main purposes: understanding complex genotype-by-environment interactions and increasing accuracy. A 2013 paper in Crop Science presented a protocol for AMMI analysis with best practices, which has four steps: (i) analysis of variance, (ii) model diagnosis, (iii) mega-environment delineation, and (iv) agricultural recommendations. This preprint announces free open-source software, called AMMISOFT, which makes it easy to implement this protocol and thereby to accelerate crop improvement.

bioinformatics↗
bioRxiv2019

Reproducible Risk Loci and Psychiatric Comorbidities in Anxiety: Results from ~200,000 Million Veteran Program Participants

We used GWAS in the Million Veteran Program sample (nearly 200,000 informative individuals) using a continuous trait for anxiety (GAD-2) to identify 5 genome-wide significant (GWS) signals for European Americans (EA) and 1 for African Americans. The strongest findings were on chromosome 3 (rs4603973, p=7.40x10-11) near the SATB1 locus, a global regulator of gene expression and on chromosome 6 (rs6557168, p=1.04x10-9) near ESR1 which encodes estrogen receptor . A locus identified on chromosome 7 near MADIL1 (p=1.62x10-8) has been previously identified in GWAS of bipolar disorder and of schizophrenia and may represent a risk factor for psychiatric disorders broadly. SNP-based heritability was estimated to be ~6% for GAD-2. We also GWASed for self-reported anxiety disorder diagnoses (N=224,330) and identified two GWS loci, one (rs35546597, MAF=0.42, p=1.88x10-8) near the AURKB locus, and the other (rsl0534613, MAF=0.41, p=4.92x10-8) near the IQCHE and MADIL1 locus identified in the GAD-2 analysis. We demonstrate reproducibility by replicating our top findings in the summary statistics from the Anxiety NeuroGenetics Study (ANGST) and a UK Biobank neuroticism GWAS. We also replicated top findings from a large UK Biobank preprint, demonstrating stability of GWAS findings in complex traits once sufficient power is attained. Finally, we found evidence of significant genetic overlap between anxiety and major depression using polygenic risk scores, but also found that the main anxiety signals are independent of those for MDD. This work presents novel insights into the neurobiological risk underpinning anxiety and related psychiatric disorders. SignificanceAnxiety disorders are common and often disabling. They are also frequently co-morbid with other mental disorders such as major depressive disorder (MDD); these disorders may share commonalities in their underlying genetic architecture. Using one of the largest homogenously phenotyped cohorts available, the Million Veteran Program sample, we investigated common variants associated with anxiety in genome-wide association studies (GWASes), using survey results from the GAD-2 anxiety scale (as a continuous trait, n=199,611), and self-reported anxiety disorder diagnosis (as a binary trait, n=224,330). This largest GWAS to date for anxiety and related traits identified numerous novel significant associations, several of which are replicated in other datasets, and allows inference of underlying biology.

genetics↗
bioRxiv2019

A decade of empirical research on research integrity: what have we (not) looked at?

In the past decades, increasing visibility of research misconduct scandals created momentum for discourses on research integrity to such an extent that the topic became a field of research itself. Yet, a comprehensive overview of research in the field is still missing. Here we describe methods, trends, publishing patterns, and impact of a decade of research on research integrity.\n\nTo give a comprehensive overview of research on research integrity, we first systematically searched SCOPUS, Web of Science, and PubMed for relevant articles published in English between 2005 and 2015. We then classified each relevant article according to its topic, several methodological characteristics, its general focus and findings, and its citation impact.\n\nWe included 986 articles in our analysis. We found that the body of literature on research integrity is growing in importance, and that the field is still largely dominated by non-empirical publications. Within the bulk of empirical records (N=342), researchers and students are most often studied, but other actors and the social context in which they interact, seem to be overlooked. The few empirical articles that examined determinants of misconduct found that problems from the research system (e.g., pressure, competition) were most likely to cause inadequate research practices. Paradoxically, the majority of empirical articles proposing approaches to foster integrity focused on techniques to build researchers awareness and compliance rather than techniques to change the research system.\n\nOur review highlights the areas, methods, and actors favoured in research on research integrity, and reveals a few blindspots. Involving non-researchers and reconnecting what is known to the approaches investigated may be the first step to generate executable knowledge that will allow us to increase the success of future approaches.\n\nA word from the authorsWe find important to mention that this manuscript underwent peer review and was rejected from the following journals:\n\nO_LIPLOS ONE\nO_LISubmitted 19th December 2017\nC_LIO_LIPeer-review and rejection received 26th June 2018.\nC_LI\nC_LIO_LIJournal of Science and Engineering Ethics (JSEE)\nO_LISubmitted 18th August 2018\nC_LIO_LIPeer-review response with major revision request received 9th September 2019\nC_LIO_LIRevision submitted 24th October 218\nC_LIO_LIRejection received 27th December 2018\nC_LI\nC_LI\n\nWe regret not having submitted this preprint before our first submission. Nonetheless, now after over one year in submission processes, we thought that we should make this manuscript and its data available as a pre-print before undergoing further submissions.\n\nIn order to promote transparency however, we asked both journal whether anonymous reviews could be added alongside this pre-print to ensure that readers are informed of the issues that disqualified our manuscript.\n\nPLOS ONE agreed for us to share the anonymous reviews which are now available -- together with our itemized changes and responses -- in the Online Resource 5 - Peer Review Report. We thank the editors of the Journal of Science and Engineering Ethics and the integrity team of Springer Nature for thoroughly discussing our request, but unfortunately, given the closed peer review policy at Springer Nature, we were unable to provide information about the peer review from the Journal of Science and Engineering Ethics.\n\nWe advise our readers to look at the peer-review and be aware of the challenges and limitations attached with our work. Of course, we welcome comments and contributions to make our work better.\n\nSincerely,\n\nNoemie Aubert Bonn and Wim Pinxten

scientific communication and education↗
bioRxiv2019

Inhibition of ADORA1 attenuates hepatic steatosis by gut microbiota-derived acetic acid from Astragalus polysaccharides

The authors have withdrawn this manuscript, because some data could not be replicated. During the process of subsequent revision of the manuscript, we separated the data into two parts. The majority data of the preprint draft, the anti-NAFLD effect of Astragalus polysaccharides (APS) in mice and the contribution of gut microbiota, were independently published in 2021 after substantial revision (doi: https://doi.org/10.1080/19490976.2021.1930874). However, the data on figure 6 (about ARs inhibitors DPCPX orally ameliorating NAFLD in mice, and Adora1 si-RNA data in vitro) could not be fully replicated in subsequent experiments. The most probable reason might be due to the batch differences of mice / cells, or other undetermined factors during experiment. Moreover, we have carried out in-depth studies on the exact role of hepatic A1R on NAFLD formation, which is opposite to our prior assumption. Therefore, we do not wish this work to be cited as reference for the project. We apologize for any inconvenience caused to our readers. Any questions can be addressed to first/corresponding author.

physiology↗
bioRxiv2019

Colour preferences of Spotted Wing Drosophila, Drosophila suzukii, under field conditions in various crops

The authors have withdrawn this manuscript because of conflicting authorship views of an unnamed person claiming authorship. Therefore, the authors do not wish this work to be cited as reference for the project.\n\nHowever, the original results of the withdrawn preprint remain valid. If you have any questions, please contact the corresponding author (Johannes.fahrentrapp@zhaw.ch).

ecology↗
bioRxiv2019

Extended Amygdala Kappa Opioid Receptor Signaling Gates Alcohol-induced Stress Impairments in Mice

"The authors have withdrawn their manuscript because they identified errors in the methods and data reporting that make the results and conclusions unreliable. The published version of this preprint has already been retracted. 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."

neuroscience↗
bioRxiv2019

UMI-VarCal: a new UMI-based variant caller that efficiently improves low-frequency variant detection in paired-end sequencing NGS libraries

1DisclaimerThe author has withdrawn version 2 of this manuscript due to a duplicate posting of manuscript number 027532. Therefore, the author does not wish this work to be cited as reference for the project. 775817v1 is the appropriate submission and the published version of the appropriate preprint can be found in the published article link. If you have any questions, please contact the corresponding author.

bioinformatics↗
bioRxiv2019

Continuous force measurements reveal no inhibitory control deficits in Parkinson’s disease

Suppression of unwanted motor responses can be disrupted by Parkinsons disease. People with Parkinsons (PwP) can show maladaptive reward-driven behaviours in the form of impulse control behaviours, which are associated with use of the dopaminergic treatments used to alleviate the motor symptoms of the disease. However, the effects of Parkinsons itself on impulsive behaviour and control are unclear - empirical studies have yielded mixed findings, and some imaging studies have shown a functional deficit in the absence of a measurable change in behaviour. Here, we investigated the effects of Parkinsons on response activation and control by studying the dynamics of response in standard inhibitory control tasks - the Stop Signal and Simon tasks - using a continuous measure of response force. Our results are largely in favour of the conclusion that response inhibition appears to be intact in PwP, even when using a more sensitive measure of behavioural control relative to traditional button-press measures. Our findings provide some clarity as to the effects of Parkinsons on response inhibition and show continuous response force measurement can provide a sensitive means of detecting erroneous response activity in PwP, which could also be generalised to studying related processes in other populations. Open dataData and analysis can be found on the Open Science Framework (osf.io/kx6h3/) Pre-print templateWiernik, B.M. (2019, October 11). Preprint templates. osf.io/hsv6a/

neuroscience↗