bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardelino: Integrating whole exomes and single-cell transcriptomes to reveal phenotypic impact of somatic variants
Authors: McCarthy Davis J. , Rostom Raghd , Huang Yuanhua , Kunz Daniel J. , Danecek Petr , Bonder Marc Jan , Hagai Tzachi ,   HipSci Consortium, Wang Wenyi , Gaffney Daniel J. , Simons Benjamin D. , Stegle Oliver , Teichmann Sarah A. 
Published: September 2018

AbstractDecoding the clonal substructures of somatic tissues sheds light on cell growth, development and differentiation in health, ageing and disease. DNA-sequencing, either using bulk or using single-cell assays, has enabled the reconstruction of clonal trees from frequency and co-occurrence patterns of somatic variants. However, approaches to systematically characterize phenotypic and functional variations between individual clones are not established. Here we present cardelino (https://github.com/PMBio/cardelino), a computational method for inferring the clone of origin of individual cells that have been assayed using single-cell RNA-seq (scRNA-seq). After validating our model using simulations, we apply cardelino to matched scRNA-seq and exome sequencing data from 32 human dermal fibroblast lines, identifying hundreds of differentially expressed genes between cells from different somatic clones. These genes are frequently enriched for cell cycle and proliferation pathways, indicating a key role for cell division genes in non-neutral somatic evolution.Key findingsA novel approach for integrating DNA-seq and single-cell RNA-seq data to reconstruct clonal substructure for single-cell transcriptomes.Evidence for non-neutral evolution of clonal populations in human fibroblasts.Proliferation and cell cycle pathways are commonly distorted in mutated clonal populations.
PISDis a mitochondrial disease gene causing skeletal dysplasia, cataracts, and white matter changes
Authors: Zhao Tian , Goedhart Caitlin M. , Sam Pingdewinde , Lingrell Susanne , Cornish Adam J. , Lamont Ryan E , Bernier Francois P , Sinasac David , Parboosingh Jillian S ,   Care4Rare Canada Consortium, Vance Jean E. , Claypool Steven M. , Innes A Micheil , Shutt Timothy E 
Published: September 2018

AbstractExome sequencing of two sisters with congenital cataracts, short stature and white matter changes identified compound heterozygous variants in thePISDgene, encoding the phosphatidylserine decarboxylase enzyme that converts phosphatidylserine (PS) to phosphatidylethanolamine (PE) in the inner mitochondrial membrane (IMM). Decreased conversion of PS to PE, and depletion of total cellular PE levels in patient fibroblasts are consistent with impaired PISD enzyme activity. Meanwhile, as evidence for mitochondrial dysfunction, patient fibroblasts exhibited more fragmented mitochondrial networks, enlarged lysosomes, decreased maximal oxygen consumption rates and increased sensitivity to 2-deoxyglucose. Moreover, treatment with lyso-PE, which can replenish the mitochondrial pool of PE, restored mitochondrial and lysosome morphology in patient fibroblasts. Functional characterization of thePISDmutations demonstrates that the maternal variant causes an alternative splice product. Meanwhile, the paternal variant impairs autocatalytic self-processing of the PISD protein required for its activity. Finally, evidence for impaired activity of mitochondrial IMM proteases explains why the phenotypes of thesePISDpatients resemble recently described “mitochondrial chaperonopathies”. Collectively, these findings demonstrate thatPISDis a novel mitochondrial disease gene.
Historical biogeography of the leopard (Panthera pardus) and its extinct Eurasian populations
Authors: Paijmans Johanna L.A. , Barlow Axel , Förster Daniel W. , Henneberger Kirstin , Meyer Matthias , Nickel Birgit , Nagel Doris , Havmøller Rasmus Worsøe , Baryshnikov Gennady F. , Joger Ulrich , Rosendahl Wilfried , Hofreiter Michael 
Published: September 2018

AbstractBackgroundResolving the historical biogeography of the leopard(Panthera pardus)is a complex issue, because patterns inferred from fossils and from molecular data lack congruence. Fossil evidence supports an African origin, and suggests that leopards were already present in Eurasia during the Early Pleistocene. Analysis of DNA sequences however, suggests a more recent, Middle Pleistocene shared ancestry of Asian and African leopards. These contrasting patterns led researchers to propose a two-stage hypothesis of leopard dispersal out of Africa: an initial Early Pleistocene colonisation of Asia and a subsequent replacement by a second colonisation wave during the Middle Pleistocene. The status of Late Pleistocene European leopards within this scenario is unclear: were these populations remnants of the first dispersal, or do the last surviving European leopards share more recent ancestry with their African counterparts?ResultsIn this study, we generate and analyse mitogenome sequences from historical samples that span the entire modern leopard distribution, as well as from Late Pleistocene remains. We find a deep bifurcation between African and Eurasian mitochondrial lineages (∼710 Ka), with the European ancient samples as sister to all Asian lineages (∼483 Ka). The modern and historical mainland Asian lineages share a relatively recent common ancestor (∼122 Ka), and we find one Javan sample nested within these.ConclusionsThe phylogenetic placement of the ancient European leopard as sister group to Asian leopards suggests that these populations originate from the same out-of-Africa dispersal which founded the Asian lineages. The coalescence time found for the mitochondrial lineages aligns well with the earliest undisputed fossils in Eurasia, and thus encourages a re-evaluation of the identification of the much older putative leopard fossils from the region. The relatively recent ancestry of all mainland Asian leopard lineages suggests that these populations underwent a severe population bottleneck during the Pleistocene. Finally, although only based on a single sample, the unexpected phylogenetic placement of the Javan leopard could be interpreted as evidence for exchange of mitochondrial lineages between Java and mainland Asia, calling for further investigation into the evolutionary history of this subspecies.
Combined effects of migration distance, foraging method vegetation density, and population density on wing shapes of boreal songbirds
Authors: Noreau Flavie , Desrochers André 
Published: September 2018

AbstractIn birds, migration distance is known to influence morphological attributes that influence flight performance, especially wing shape. However, wing shape is under the likely influence of less documented factors such as foraging method, vegetation density and isolation of individuals and populations. To better understand factors leading to interspecific differences in wing shape, we measured the pointedness of wings (Kipp’s distance) of 1017 live birds of 22 species in an eastern Canadian boreal forest. We modeled wing pointedness as a function of migration distances from eBird records, foraging, habitat, and population density data fromBirds of North Americamonographs. Long-distance migrants and species living in low-density vegetation had more pointed wings than shorter-distance migrants and dense-vegetation dwellers, in accordance to our predictions. After accounting for vegetation density and migration distance, we found no link between the extent of aerial foraging or mean breeding population density, an indicator of isolation, and wing pointedness. Those results are consistent with a tradeoff between sustained flight efficiency and maneuverability, but suggest that interspecific variation in wing shape due specifically to foraging method or habitat isolation is nonexistent or obscured by other factors.
An Open-Source Plate Reader
Authors: Szymula Karol , Magaraci Michael S. , Patterson Michael , Clark Andrew , Mannickarottu Sevile G. , Chow Brian Y. 
Published: September 2018

AbstractMicroplate readers are foundational instruments in experimental biology and bioengineering that enable multiplexed spectrophotometric measurements. To enhance their accessibility, we here report the design, construction, validation, and benchmarking of an open-source microplate reader. The system features full-spectrum absorbance and fluorescence emission detection, in situ optogenetic stimulation, and stand-alone touch screen programming of automated assay protocols. The total system costs <$3500, a fraction of the cost of commercial plate readers, and can detect the fluorescence of common dyes down to ∼10 nanomolar concentration. Functional capabilities were demonstrated in context of synthetic biology, optogenetics, and photosensory biology: by steady-state measurements of ligand-induced reporter gene expression in a model of bacterial quorum sensing, and by flavin photocycling kinetic measurements of a LOV (light-oxygen-voltage) domain photoreceptor used for optogenetic transcriptional activation. Fully detailed guides for assembling the device and automating it using the custom Python-based API (Application Program Interface) are provided. This work contributes a key technology to the growing community-wide infrastructure of open-source biology-focused hardware, whose creation is facilitated by rapid prototyping capabilities and low-cost electronics, optoelectronics, and microcomputers.Table of Contents Graphic:
Molecular Subtyping reveals Immune Alterations associated with Progression of Bronchial Premalignant Lesions
Authors: Beane Jennifer , Mazzilli Sarah A. , Campbell Joshua D. , Duclos Grant , Krysan Kostyantyn , Moy Christopher , Perdomo Catalina , Schaffer Michael , Liu Gang , Zhang Sherry , Liu Hangqio , Vick Jessica , Dhillon Samjot S. , Platero Suso J. , Dubinett Steven M. , Stevenson Christopher , Reid Mary E. , Lenburg Marc E. , Spira Avrum E. 
Published: September 2018

AbstractBronchial premalignant lesions (PMLs) are precursors of lung squamous cell carcinoma, but have variable outcome, and we lack tools to identify and treat PMLs at highest risk for progression to invasive cancer. Profiling endobronchial biopsies of PMLs obtained from high-risk smokers by RNA-Seq identified four PML subtypes with differences in epithelial and immune processes. One molecular subtype (Proliferative) is enriched with dysplastic lesions and exhibits up-regulation of metabolic and cell cycle pathways and down-regulation of ciliary processes. RNA-Seq profiles from normal-appearing uninvolved large airway brushings could identify subjects with Proliferative lesions with high specificity. Expression of interferon signaling and antigen processing/presentation pathways are decreased in progressive/persistent Proliferative lesions and immunofluorescence indicates a depletion of innate and adaptive immune cells in these lesions. Molecular biomarkers measured in PMLs or the uninvolved airway can enhance histopathological grading and suggests that immunoprevention strategies may be effective in intercepting the progression of PMLs to lung cancer.
Increasing metadata coverage of SRA BioSample entries using deep learning based Named Entity Recognition
Authors: Klie Adam , Tsui Brian Y , Mollah Shamim , Skola Dylan , Dow Michelle , Hsu Chun-Nan , Carter Hannah 
Published: September 2018

AbstractHigh quality metadata annotations for data hosted in large public repositories are essential for research reproducibility, and for conducting fast, powerful and scalable meta-analyses. Currently, a majority of sequencing samples in the National Center for Biotechnology Information’s (NCBI’s) Sequence Read Archive (SRA) are missing metadata across several categories. In an effort to improve the metadata coverage of these samples, we leveraged almost 44 million attribute-value pairs from SRA BioSample to train a scalable, recurrent neural network that predicts missing metadata via Named Entity Recognition (NER). The network was first trained to classify short text phrases according to 11 metadata categories and achieved an overall accuracy and area under the receiver operating characteristic (AUROC) curve of 85.2% and 0.977 respectively. We then applied our classifier to predict 11 metadata categories from the longer TITLE attribute of samples, evaluating performance on a set of samples withheld from model training. Prediction accuracies were high when extracting sample Species (94.85%), Condition/Disease (95.65%) and Strain (82.03%) from TITLEs, with lower accuracies and lack of predictions for other categories highlighting multiple issues with the current metadata annotations in BioSample. These results indicate the utility of recurrent neural networks for NER-based metadata prediction and the potential for models such as the one presented here to increase metadata coverage in BioSample while minimizing the need for manual curation.AvailabilityAll the analyses, environments, and Jupyter notebooks pertaining to this manuscript are available on Github: https://github.com/cartercompbio/PredictMEE.
Distinct evolutionary dynamics of horizontal gene transfer in drug resistant and virulent clones ofKlebsiella pneumoniae
Authors: Wyres Kelly L , Wick Ryan R , Judd Louise M , Froumine Roni , Tokolyi Alex , Gorrie Claire L , Lam Margaret M C , Duchêne Sebastián , Jenney Adam , Holt Kathryn E 
Published: September 2018

AbstractKlebsiella pneumoniae(Kp) has emerged as an important cause of two distinct public health threats: multidrug resistant (MDR) healthcare-associated infections1and community-acquired invasive infections, particularly pyogenic liver abscess2. The majority of MDR hospital outbreaks are caused by a subset ofKpclones with a high prevalence of acquired antimicrobial resistance (AMR) genes, while the majority of community-acquired invasive infections are caused by ‘hypervirulent’ clones that rarely harbour acquired AMR genes but have high prevalence of key virulence loci3–5. Worryingly, the last few years have seen increasing reports of convergence of MDR and the key virulence genes within individualKpstrains6, but it is not yet clear whether these represent a transient phenomenon or a significant ongoing threat. Here we perform comparative genomic analyses for 28 distinctKpclones, including 6 hypervirulent and 8 MDR, to better understand their evolutionary histories and the risks of convergence. We show that MDR clones are highly diverse with frequent chromosomal recombination and gene content variability that far exceeds that of the hypervirulent clones. Consequently, we predict a much greater risk of virulence gene acquisition by MDRKpclones than of resistance gene acquisition by hypervirulent clones.
Structural basis for recruitment of DAPK1 to the KLHL20 E3 ligase
Authors: Chen Zhuoyao , Picaud Sarah , Filippakopoulos Panagis , D’Angiolella Vincenzo , Bullock Alex N. 
Published: September 2018

SUMMARYBTB-Kelch proteins form the largest subfamily of Cullin-RING E3 ligases, yet their substrate complexes are mapped and structurally characterized only for KEAP1 and KLHL3. KLHL20 is a related CUL3-dependent ubiquitin ligase linked to autophagy, cancer and Alzheimer’s disease that promotes the ubiquitination and degradation of substrates including DAPK1, PML and ULK1. We identified a ‘LPDLV’-containing recruitment site in the DAPK1 death domain and determined the 1.1 Å crystal structure of a KLHL20-DAPK1 complex. DAPK1 binds to KLHL20 as a loose helical turn that inserts deeply into the central pocket of the Kelch domain to contact all six blades of the β-propeller. Here, KLHL20 forms a salt bridge as well as hydrophobic interactions that include a tryptophan and cysteine residue ideally positioned for covalent inhibitor development. The structure highlights the diverse binding modes of circular substrate pockets versus linear grooves and suggests a novel E3 ligase for protac-based drug design.
Analysis of a large data set reveals haplotypes carrying putatively recessive lethal alleles with pleiotropic effects on economically important traits in beef cattle
Authors: Jenko Janez , McClure Matthew C , Matthews Daragh , McClure Jennifer , Johnsson Martin , Gorjanc Gregor , Hickey John M 
Published: September 2018

AbstractBackgroundDeleterious recessive alleles can result in reduced economic performance in livestock in multiple ways in homozygous individuals: from early embryonic death, death soon after birth, to being non-lethal but causing reduced viability. While death is an easy phenotype to score, reduced viability is not as easy to identify. However, it can sometimes be observed as reduced artificial insemination (AI) conception rates, longer calving intervals, or higher hazard for live born animals.MethodsIn this paper, we searched for haplotypes carrying putatively recessive lethal alleles in 132,725 genotyped Irish beef cattle from five breeds: Aberdeen Angus, Charolais, Hereford, Limousin, and Simmental. We phased the genotypes in sliding windows along the genome and used five tests to identify haplotypes with absence of or reduced homozygosity. We then corroborated the identified haplotypes with reproduction records, indicating early embryonic death, and postnatal survival records. Finally, we assessed haplotype pleiotropy by estimating substitution effects on national estimates of breeding values for 15 economically important traits in beef production.ResultsWe found support for three haplotypes with carrying putatively recessive lethal alleles. The haplotypes were located on chromosome 14 in Aberdeen Angus, chromosome 19 in Charolais and chromosome 16 in Simmental. Their population frequencies is 15.2%, 14.4%, and 8.8%, respectively. All of the haplotypes showed pleiotropic effects on economically important traits for beef production. Their allele substitution effects are €3.23, €1.47, and €2.30 for the terminal index and -€3.15, -€0.75, and €1.12 for the replacement index, where one standard deviations are €18.32, €22.54, and €22.33 for terminal index and €29.52, €35.62, and €30.97 for the replacement index. We identified ZFAT as the candidate gene for lethality in Aberdeen Angus, several candidate genes for the Simmental haplotype, and no candidate genes for the Charolais haplotype.ConclusionsWe analysed genotype, reproduction, survival, and production data to discover haplotypes carrying putatively recessive lethal alleles in Irish beef cattle. We found support for three haplotypes. All three haplotypes have pleiotropic effects on economically important traits in beef production.
Differential impact of endogenous and exogenous attention on activity in human visual cortex
Authors: Dugué Laura , Merriam Elisha P. , Heeger David J. , Carrasco Marisa 
Published: September 2018

ABSTRACTHow do endogenous (voluntary) and exogenous (involuntary) attention modulate activity in visual cortex? Using ROI-based fMRI analysis, we measured fMRI activity for valid and invalid trials (target at cued/un-cued location, respectively), pre- or post-cueing endogenous or exogenous attention, while participants performed the same orientation discrimination task. We found stronger modulation in contralateral than ipsilateral visual regions, and higher activity in valid-than invalid-trials. For endogenous attention, modulation of stimulus-evoked activity due to a pre-cue increased along the visual hierarchy, but was constant due to a post-cue. For exogenous attention, modulation of stimulus-evoked activity due to a pre-cue was constant along the visual hierarchy, but was not modulated due to a post-cue. These findings reveal that endogenous and exogenous attention distinctly modulate activity in visuo-occipital areas during orienting and reorienting; endogenous attention facilitates both the encoding and the readout of visual information whereas exogenous attention only facilitates the encoding of information.
Overestimation of the prevalence of eosinophilic colitis with reliance on a single billing code
Authors: Muir AB , Jensen ET , Wechsler JB , Menard-Katcher P , Falk GW , Aceves SS , Furuta GT , Dellon ES , Rothenberg ME , Spergel JM 
Published: September 2018

AbstractEosinophilic colitis (EC) is a rare disorder characterized by eosinophilic inflammation of the colon causing diarrhea, bloody stool, nausea, constipation and abdominal pain. The Consortium for Eosinophilic Gastrointestinal Disease Research sought to undertake the first multi-center study of the EC population, but faced challenges with meeting enrollment goals that were based on initial estimates. To understand the reason for this, we performed chart review of patients with ICD codes for EC at 8 tertiary care centers. Chart review revealed that the isolated use of ICD codes overestimated EC rates in the pediatric population.
Neural responses to heartbeats as a mechanism for distinguishing self from other during imagination
Authors: Babo-Rebelo Mariana , Buot Anne , Tallon-Baudry Catherine 
Published: September 2018

AbstractImagination is an internally-generated process, where one can make oneself or other people appear as protagonists of a scene. How does the brain tag the protagonist of an imagined scene, as being oneself or someone else? Crucially, neither external stimuli nor motor feedback are available during imagination to disentangle imagining oneself from imagining someone else. Here, we test the hypothesis that an internal mechanism based on the neural monitoring of heartbeats could distinguish between self and other. 23 participants imagined themselves (from a first-person perspective) or a friend (from a third-person perspective) in various scenarios, while their brain activity was recorded with magnetoencephalography and their cardiac activity was simultaneously monitored. We measured heartbeat-evoked responses, i.e. transients of neural activity occurring in response to each heartbeat, during imagination. The amplitude of heartbeat-evoked responses differed between imagining oneself and imagining a friend, in the precuneus, mid and posterior cingulate regions bilaterally. Effect size was modulated by the general daydreaming frequency of participants but not by their interoceptive abilities. These results could not be accounted for by other characteristics of imagination (e.g., the ability to adopt the perspective, valence or arousal), nor by cardiac parameters (e.g., heart rate) or arousal levels. Heartbeat-evoked responses thus appear as a neural marker distinguishing self from other during imagination.Highlights- Heartbeat-evoked responses differentiate self from other during imagination.- These effects were located in the precuneus and mid- to posterior cingulate.- The neural monitoring of the body could be a mechanism for self/other distinction.
DeepProteomics: Protein family classification using Shallow and Deep Networks
Authors: Vazhayil Anu , Vinayakumar R , Soman KP 
Published: September 2018

ABSTRACTThe knowledge regarding the function of proteins is necessary as it gives a clear picture of biological processes. Nevertheless, there are many protein sequences found and added to the databases but lacks functional annotation. The laboratory experiments take a considerable amount of time for annotation of the sequences. This arises the need to use computational techniques to classify proteins based on their functions. In our work, we have collected the data from Swiss-Prot containing 40433 proteins which is grouped into 30 families. We pass it to recurrent neural network(RNN), long short term memory(LSTM) and gated recurrent unit(GRU) model and compare it by applying trigram with deep neural network and shallow neural network on the same dataset. Through this approach, we could achieve maximum of around 78% accuracy for the classification of protein families.