bluuebunny/crossref_metadata_2025_split huggingface dataset:
Broad geographic sampling reveals predictable, pervasive, and strong seasonal adaptation inDrosophila
Authors: Machado Heather E. , Bergland Alan O. , Taylor Ryan , Tilk Susanne , Behrman Emily , Dyer Kelly , Fabian Daniel K. , Flatt Thomas , González Josefa , Karasov Talia L. , Kim Bernard , Kozeretska Iryna , Lazzaro Brian P. , Merritt Thomas JS , Pool John E. , O’Brien Katherine , Rajpurohit Subhash , Roy Paula R. , Schaeffer Stephen W. , Serga Svitlana , Schmidt Paul , Petrov Dmitri A. 
Published: June 2018

AbstractTo advance our understanding of adaptation to temporally varying selection pressures, we identified signatures of seasonal adaptation occurring in parallel amongDrosophila melanogasterpopulations. Specifically, we estimated allele frequencies genome-wide from flies sampled early and late in the growing season from 20 widely dispersed populations. We identified parallel seasonal allele frequency shifts across North America and Europe, demonstrating that seasonal adaptation is a general phenomenon of temperate fly populations. Seasonally fluctuating polymorphisms are enriched in large chromosomal inversions and we find a broad concordance between seasonal and spatial allele frequency change. The direction of allele frequency change at seasonally variable polymorphisms can be predicted by weather conditions in the weeks prior to sampling, linking the environment and the genomic response to selection. Our results suggest that fluctuating selection is an important evolutionary force affecting patterns of genetic variation inDrosophila.
Molecular evolution of juvenile hormone esterase-like proteins in a socially exchanged fluid
Authors: LeBoeuf Adria C. , Cohanim Amir B. , Stoffel Céline , Brent Colin S. , Waridel Patrice , Privman Eyal , Keller Laurent , Benton Richard 
Published: June 2018

AbstractSocially exchanged fluids are a direct means for organisms to influence conspecifics. When orally feeding larval offspring via trophallaxis, Camponotus floridanus ant workers were shown to transfer Juvenile Hormone (JH), a key developmental regulator, as well as paralogs of JH esterase (JHE), an enzyme that hydrolyzes JH. We combine proteomic, phylogenetic and selection analyses to investigate the evolution of this esterase subfamily. We show that Camponotus JHE-like proteins have sustained multiple duplications, positive selection, and changed localization to become abundantly and selectively present in trophallactic fluid. To assess their potential role in larval development, we fed workers a JHE-specific inhibitor to introduce it into the trophallactic network. This increased the proportion larvae reared to metamorphosis by these workers, similar to supplementation with JH. Together these findings suggest that JHE-like proteins have evolved new roles in inter-individual regulation of larval development in Camponotus.
Combining Multi-Site/Multi-Study MRI Data: Linked-ICA Denoising for Removing Scanner and Site Variability from Multimodal MRI Data
Authors: Li Huanjie , Smith Stephen M. , Gruber Staci , Lukas Scott E. , Silveri Marisa M. , Hill Kevin P. , S Killgore William D. , Nickerson Lisa D. 
Published: June 2018

AbstractLarge multi-site studies that pool magnetic resonance imaging (MRI) data across research sites or studies, or that utilize shared data from imaging repositories, present exceptional opportunities to advance neuroscience and enhance reproducibility of neuroimaging research. However, both scanner and site variability are confounds that hinder pooling data collected across different sites or across different operating systems on the same scanner, even when all acquisition protocols are harmonized. These confounds degrade statistical analyses and can lead to spurious findings. Unfortunately, methods to address this problem are scant. In this study, we propose a novel denoising approach for multi-site multimodal MRI data that implements a data-driven linked independent component analysis (LICA) to efficiently identify scanner/site-related effects for removal. Removing these effects results in denoised data that can then be combined across sites/studies to improve modality-specific statistical processing. We use data from six different studies collected on the same scanner across major hardware (gradient and head coil) and software upgrades to demonstrate our LICA-based denoising approach. The proposed method is superior compared to the existing methods we tested and has great potential for large-scale multi-site studies to produce combined data free from study/site confounds.
FADU: A Feature Counting Tool for Prokaryotic RNA-Seq Analysis
Authors: Chung Matthew , Adkins Ricky S. , Shetty Amol C. , Sadzewicz Lisa , Tallon Luke J. , Fraser Claire M. , Rasko David A. , Mahurkar Anup , Dunning Hotopp Julie C. 
Published: June 2018

AbstractMotivationThe major algorithms for quantifying transcriptomics data for differential gene expression analysis were designed for analyzing data from human or human-like genomes, specifically those with single gene transcripts and distinct transcriptional boundaries that extend beyond the coding sequence (CDS) as identified through expressed sequence tags (ESTs) or EST-like sequence data. Some eukaryotic genomes and all, or nearly all, bacterial genomes require alternate methods of quantification since they lack annotation of transcriptional boundaries with EST or EST-like data, have overlapping transcriptional boundaries, and/or have polycistronic transcripts.ResultsAn algorithm was developed and tested that better quantifies transcriptomics data for differential gene expression analysis in organisms with overlapping transcriptional units and polycistronic transcripts. Using data from standard libraries originating from Escherichia coli and Ehrlichia chaffeensis, and strand-specific libraries from the Wolbachia endosymbiont wBm, FADU can derive counts for genes that are missed by HTSeq and featurecounts. Using the default parameters with the E. coli data, FADU can detect transcription of 51 more genes than HTSeq in union mode and 21 genes more than featurecounts, with 42 and 18 of these features being <300 bp, respectively. Due to its ability to derive counts for otherwise unrepresented genes without overstating their abundance, we believe FADU to be an improved tool for quantifying transcripts in prokaryotic systems for RNA-Seq analyses.Availability and implementationFADU is available at https://github.com/adkinsrs/FADU. FADU was implemented using Python3 and requires the PySAM module (version 0.12.0.1 or later).Contactjdhotopp@som.umaryland.edu
Codon stabilization coefficient as an index for prediction of codon bias and its potential applications
Authors: Carneiro Rodolofo L. , Requião Rodrigo D. , Rossetto Silvana , Domitrovic Tatiana , Palhano Fernando L. 
Published: June 2018

SummaryDifferent methods of mRNA half-life measurements are available, but genome-wide measurements of mRNA half-life in yeast showed a weak correlation between the methods. Moreover, when we compared mRNA half-life determined by these methods with other cellular measurements such as mRNA and protein abundance low correlation was found. To clarify this matter, we analyzed mRNA half-life datasets from nine different groups to determine the most accurate method of measurement. Since codon optimality is one of the significant determinants of mRNA stability, we used the codon stabilization coefficient (CSC) as a reference for mRNA half-life measurement accuracy. After CSC calculation for each dataset, we find strong positive correlations between the CSC from some datasets with other parameters that reflect codon optimality such as tRNA abundance and ribosome residence time. By the use of CSC parameter, we observed that most genes contain non-optimal codons and that codon bias exists toward optimized and non-optimized genes. We also observed that stretches of non-optimal are not randomly distributed since it causes impacts on translation.
Cryo-EM structure of the benzodiazepine-sensitive α1β1γ2 heterotrimeric GABAAreceptor in complex with GABA illuminates mechanism of receptor assembly and agonist binding
Authors: Phulera Swastik , Zhu Hongtao , Yu Jie , Claxton Derek P. , Yoder Nate , Yoshioka Craig , Gouaux Eric 
Published: June 2018

ABSTRACTFast inhibitory neurotransmission in the mammalian nervous system is largely mediated by GABAAreceptors, chloride-selective members of the superfamily of pentameric Cys-loop receptors. Native GABAAreceptors are heteromeric assemblies sensitive to many important drugs, from sedatives to anesthetics and anticonvulsive agents, with mutant forms of GABAAreceptors implicated in multiple neurological diseases, including epilepsy. Despite the profound importance of heteromeric GABAAreceptors in neuroscience and medicine, they have proven recalcitrant to structure determination. Here we present the structure of the triheteromeric α1β1γ2EMGABAAreceptor in complex with GABA, determined by single particle cryo-EM at 3.1-3.8 Å resolution, elucidating the molecular principles of receptor assembly and agonist binding. Remarkable N-linked glycosylation on the α1 subunit occludes the extracellular vestibule of the ion channel and is poised to modulate receptor assembly and perhaps ion channel gating. Our work provides a pathway to structural studies of heteromeric GABAAreceptors and a framework for the rational design of novel therapeutic agents.
A critical assessment of data quality and venous effects in ultra-high-resolution fMRI
Authors: Kay Kendrick , Jamison Keith W. , Vizioli Luca , Zhang Ruyuan , Margalit Eshed , Ugurbil Kamil 
Published: June 2018

AbstractAdvances in hardware, pulse sequences, and reconstruction techniques have made it possible to perform functional magnetic resonance imaging (fMRI) at sub-millimeter resolution while maintaining high spatial coverage and acceptable signal-to-noise ratio. Here, we examine whether ultra-high-resolution fMRI can be exploited for routine use in neuroscience research. We conducted fMRI in human visual cortex during a simple event-related visual experiment (7T, gradient-echo EPI, 0.8-mm isotropic voxels, 2.2-s sampling rate, 84 slices), and developed analysis and visualization tools to assess the quality of the data. We make three main observations. First, we find that the acquired fMRI images, combined with appropriate surface-based processing, provide reliable and accurate measurements of fine-scale blood oxygenation level dependent (BOLD) activity patterns. Second, we show that the highly folded structure of cortex causes substantial biases on spatial resolution and data visualization. Third, we examine the well-recognized issue of venous contributions to fMRI signals. In a systematic assessment of large sections of cortex measured at a fine scale, we show that time-averaged T2*-weighted EPI intensity is a simple, robust marker of venous effects. These venous effects are unevenly distributed across cortex, are more pronounced in gyri and outer cortical depths, and are, to a certain degree, in consistent locations across subjects relative to cortical folding. Furthermore, we show that these venous effects are strongly correlated with BOLD responses evoked by the experiment. We conclude that ultra-high-resolution fMRI can provide robust information about fine-scale BOLD activity patterns, but special care must be exercised in visualizing and interpreting these patterns, especially with regards to the confounding influence of the brain’s vasculature. To help translate these methodological findings to neuroscience research, we provide practical suggestions for both high-resolution and standard-resolution fMRI studies.
Genomic meta-analysis of the interplay between 3D chromatin organization and gene expression programs under basal and stress conditions
Authors: Nurick Idan , Shamir Ron , Elkon Ran 
Published: June 2018

AbstractBackgroundOur appreciation of the critical role of the 3D organization of the genome in gene regulation is steadily increasing. Recent 3C-based deep sequencing techniques elucidated a hierarchy of structures that underlie the spatial organization of the genome in the nucleus. At the top of this hierarchical organization are chromosomal territories and the megabase-scale A/B compartments that correlate with transcriptional activity within cells. Below them are the relatively cell-type invariant topologically associated domains (TADs), characterized by high frequency of physical contacts between loci within the same TAD and are assumed to function as regulatory units. Within TADs, chromatin loops bring enhancers and target promoters to close spatial proximity. Yet, we still have only rudimentary understanding how differences in chromatin organization between different cell types affect cell-type specific gene expression programs that are executed under basal and challenged conditions.ResultsHere, we carried out a large-scale meta-analysis that integrated Hi-C data from thirteen different cell lines and dozens of ChIP-seq and RNA-seq datasets measured on these cells, either under basal conditions or after treatment. Pairwise comparisons between cell lines demonstrated the strong association between modulation of A/B compartmentalization, differential gene expression and transcription factor (TF) binding events. Furthermore, integrating the analysis of transcriptomes of different cell lines in response to various challenges, we show that 3D organization of cells under basal conditions constrains not only gene expression programs and TF binding profiles that are active under the basal condition but also those induced in response to treatment.ConclusionsOur results further elucidate the role of dynamic genome organization in regulation of differential gene expression between different cell types, and indicate the impact of intra-TAD enhancer-promoter interactions that are established under basal conditions on both the basal and treatment-induced gene expression programs.
circuitSNPs: Predicting genetic effects using a Neural Network to model regulatory modules of DNase-seq footprints
Authors: Shanku Alexander G. , Findley Anthony , Kalita Cynthia , Shim Heejung , Luca Francesca , Pique-Regi Roger 
Published: June 2018

AbstractMotivationIdentifying and characterizing the function of non coding regions in the genome, and the genetic variants disrupting gene regulation, is a challenging question in genetics. Through the use of high throughput experimental assays that provide information about the chromatin state within a cell, coupled with modern computational approaches, much progress has been made towards this goal, yet we still lack a comprehensive characterization of the regulatory grammar. We propose a new method that combines sequence and chromatin accessibility information through a neural network framework with the goal of determining and annotating the effect of genetic variants on regulation of chromatin accessibility and gene transcription. Importantly, our new approach can consider multiple combinations of transcription factors binding at the same location when assessing the functional impact of non-coding genetic variation.ResultsOur method, circuitSNPs, generates predictions describing the functional effect of genetic variants on local chromatin accessibility. Further, we demonstrate that circuitSNPs not only performs better than other variant annotation tools, but also retains the causal motifs / transcription factors that drive the predicted regulatory effect.Contactfluca@wayne.edu, rpique@wayne.eduAvailabilityhttp://github.com/piquelab/circuitSNPs
Functional testing of a humanPBX3variant in zebrafish reveals a potential modifier role in congenital heart defects
Authors: Farr Gist H. , Imani Kimia , Pouv Darren , Maves Lisa 
Published: June 2018

AbstractWhole-genome and whole-exome sequencing efforts are increasingly identifying candidate genetic variants associated with human disease. However, predicting and testing the pathogenicity of a genetic variant remains challenging. Genome editing allows for the rigorous functional testing of human genetic variants in animal models. Congenital heart defects (CHDs) are a prominent example of a human disorder with complex genetics. An inherited sequence variant in the humanPBX3gene (PBX3p.A136V) has previously been shown to be enriched in a CHD patient cohort, indicating that thePBX3p.A136V variant could be a modifier allele for CHDs.PBXgenes encode TALE (Three Amino acid Loop Extension)-class homeodomain-containing DNA-binding proteins with diverse roles in development and disease and are required for heart development in mouse and zebrafish. Here we use CRISPR-Cas9 genome editing to directly test whether thisPBXgene variant acts as a genetic modifier in zebrafish heart development. We used a single-stranded oligodeoxynucleotide to precisely introduce the humanPBX3p.A136V variant in the homologous zebrafishpbx4gene (pbx4p.A131V). We find that zebrafish that are homozygous forpbx4p.A131V are viable as adults. However, we show that thepbx4p.A131V variant enhances the embryonic cardiac morphogenesis phenotype caused by loss of the known cardiac specification factor, Hand2. Our study is the first example of using precision genome editing in zebrafish to demonstrate a function for a human disease-associated single nucleotide variant of unknown significance. Our work underscores the importance of testing the roles of inherited variants, not justde novovariants, as genetic modifiers of CHDs. Our study provides a novel approach toward advancing our understanding of the complex genetics of CHDs.Summary statementOur study provides a novel example of using genome editing in zebrafish to demonstrate how a human DNA sequence variant of unknown significance may contribute to the complex genetics of congenital heart defects.
Benchmark and integration of resources for the estimation of human transcription factor activities
Authors: Garcia-Alonso Luz , Ibrahim Mahmoud M , Turei Denes , Saez-Rodriguez Julio 
Published: June 2018

ABSTRACTPrediction of transcription factor (TF) activities from the gene expression of their targets (i.e. TF regulon) is becoming a widely-used approach to characterize the functional status of transcriptional regulatory circuits. Several strategies and datasets have been proposed to link the target genes likely regulated by a TF, each one providing a different level of evidence. The most established ones are: (i) manually curated repositories, (ii) interactions derived from ChIP-seq binding data, (iii) in silico prediction of TF binding on gene promoters, and (iv) reverse-engineered regulons from large gene expression datasets. However, it is not known how these different sources of regulons affect the TF activity estimations, and thereby downstream analysis and interpretation. Here we compared the accuracy and biases of these strategies to define human TF regulons by means of their ability to predict changes in TF activities in three reference benchmark datasets. We assembled a collection of TF-target interactions among 1,541 TFs, and evaluated how the different molecular and regulatory properties of the TFs, such as the DNA-binding domain, specificities or mode of interaction with the chromatin, affect the predictions of TF activity changes. We assessed their coverage and found little overlap on the regulons derived from each strategy and better performance by literature-curated information followed by ChIP-seq data. We provide an integrated resource of all TF-target interactions derived through these strategies with a confidence score, as a resource for enhanced prediction of TF activities.
Individual based genetic analyses support asexual hydrochory dispersal in Zostera noltei
Authors: Berković Buga , Coelho Nelson , Gouveia Licínia , Serrão Ester A. , Alberto Filipe 
Published: June 2018

AbstractDispersal beyond the local patch in clonal plants was typically thought to result from sexual reproduction via seed dispersal. However, evidence for the separation, transport by water, and re-establishment of asexual propagules (asexual hydrochory) is mounting suggesting other important means of dispersal in aquatic plants. Using an unprecedented sampling size and microsatellite genetic identification, we describe the distribution of seagrass clones along tens of km within a coastal lagoon in Southern Portugal. Our spatially explicit individual-based sampling design covered 84 km2 and collected 3 185 Zostera noltei ramets from 803 sites. We estimated clone age, assuming rhizome elongation as the only mechanism of clone spread, and contrasted it with paleo-oceanographic sea level change. We also studied the association between a source of disturbance and the location of large clones. A total of 16 clones were sampled more than 10 times and the most abundant one was sampled 59 times. The largest distance between two samples from the same clone was 26.4 km and a total of 58 and 10 clones were sampled across more than 2 and 10 km, respectively. The number of extremely large clone sizes, and their old ages when assuming the rhizome elongation as the single causal mechanism, suggests other processes are behind the span of these clones. We discuss how the dispersal of vegetative fragments in a stepping-stone manner might have produced this pattern. We found higher probabilities to sample large clones away from the lagoon inlet, considered a source of disturbance. This study corroborates previous experiments on the success of transport and re-establishment of asexual fragments and supports the hypothesis that asexual hydrochory is responsible for the extent of these clones.