bluuebunny/crossref_metadata_2025_split huggingface dataset:
DeepSV: Accurate calling of genomic deletions from high-throughput sequencing data using deep convolutional neural network
Authors: Cai Lei , Wu Yufeng , Gao Jingyang 
Published: February 2019

AbstractBackgroundCalling genetic variations from sequence reads is an important problem in genomics. There are many existing methods for calling various types of variations. Recently, Google developed a method for calling single nucleotide polymorphisms (SNPs) based on deep learning. Their method visualizes sequence reads in the forms of images. These images are then used to train a deep neural network model, which is used to call SNPs. This raises a research question: can deep learning be used to call more complex genetic variations such as structural variations (SVs) from sequence data?ResultsIn this paper, we extend this high-level approach to the problem of calling structural variations. We present DeepSV, an approach based on deep learning for calling long deletions from sequence reads. DeepSV is based on a novel method of visualizing sequence reads. The visualization is designed to capture multiple sources of information in the sequence data that are relevant to long deletions. DeepSV also implements techniques for working with noisy training data. DeepSV trains a model from the visualized sequence reads and calls deletions based on this model. We demonstrate that DeepSV outperforms existing methods in terms of accuracy and efficiency of deletion calling on the data from the 1000 Genomes Project.ConclutionsOur work shows that deep learning can potentially lead to effective calling of different types of genetic variations that are complex than SNPs.Availability and implementationDeepSV’s source code and sample result as part of this project are readily available from GitHub at https://github.com/CSuperlei/DeepSV/.
Diurnal variations in serum metabolites of wintering redheaded buntings
Authors: Gupta Neelu Jain , Das Samya , Das Mrinal , Arya Rakesh , Nanda Ranjan Kumar 
Published: February 2019

ABSTRACTDaily behavioural and physiological changes in bird may reflect in biofluid metabolite composition. Locomotor activity, food intake and body temperature of group (n=7) of male migratory redheaded buntings held under short days (8L:16D, SD) were monitored besides blood sampling at midday (ZT4: 4 hours zeitgeber time starting ZT0 as lights ‘on’) and midnight (ZT16). The birds exhibited higher activity and increased feeding during daytime with negligible activity and feeding at night. Gas chromatography mass spectrometry and chemo-metric analyses of bird serum revealed higher levels of lipid (palmitic, oleic and linoleic acids) and protein (uric acid and proline) catabolites in daytime serum samples as compared to night samples. Higher night-time levels of short chain fatty acids indicated utilization of glucose and lipolysis in night fasted birds. High night-time levels of taurine, a sulphur amino acid has adaptive advantage to night migratory song birds. The diurnal differences in metabolite patterns suggests differential energy expenditure during day and renders survival benefit to buntings as night migrants. We propose a GCMS method that could be useful to unravel different annual life-history stages including migration.
An early Myc-dependent transcriptional program underlies enhanced macromolecular biosynthesis and cell growth during B-cell activation
Authors: Tesi Alessandra , Pretis Stefano de , Furlan Mattia , Filipuzzi Marco , Morelli Marco J. , Andronache Adrian , Doni Mirko , Verrecchia Alessandro , Pelizzola Mattia , Amati Bruno , Sabò Arianna 
Published: February 2019

AbstractUpon activation, lymphocytes exit quiescence and undergo substantial increases in cell size, accompanied by activation of energy-producing and anabolic pathways, widespread chromatin decompaction and elevated transcriptional activity. These changes depend upon prior induction of the Myc transcription factor, but how Myc controls them remains unclear. We addressed this issue in primary mouse B-cells, based on conditional deletion of the c-myc gene, followed by LPS stimulation. Myc was rapidly induced, became detectable on virtually all active promoters and enhancers, but had no direct impact on global transcriptional activity. Instead, Myc contributed to the swift up- and down-regulation of several hundred genes, including many known regulators of the aforementioned cellular processes. Myc-activated promoters were enriched for E-box consensus motifs, bound Myc at the highest levels and showed enhanced RNA Polymerase II recruitment, the opposite being true at down-regulated loci. Remarkably, the Myc-dependent signature identified in activated B-cells was also enriched in Myc-driven B-cell lymphomas: hence, besides modulation of new cancer-specific programs, the oncogenic action of Myc may largely rely on sustained deregulation of its normal physiological targets.
Dual Acting Small-Molecule Inhibitors Targeting Mycobacterial DNA Replication
Authors: Singh Meenakshi , Ilic Stefan , Tam Benjamin , Ben-Ishay Yasmin , Sherf Dror , Pappo Doron , Akabayov Barak 
Published: February 2019

AbstractMycobacterium tuberculosis(Mtb) is a pathogenic bacterium and a causative agent of tuberculosis (TB), a disease that kills more than 1.5 million people worldwide annually. One of the main reasons for this high mortality rate is the evolution of newMtbstrains that are resistant to available antibiotics. Therefore, new therapeutics for TB are in constant demand. Here we report the development of such inhibitors that target two DNA replication enzymes ofMtb, namely DnaG primase and DNA gyrase, which share a conserved TOPRIM fold near the inhibitors’ binding site. The molecules were developed on the basis of previously reported inhibitors for T7 DNA primase that bind near the TOPRIM fold. In order to improve the physicochemical properties of the molecules as well as their inhibitory effect on primase and gyrase, 49 novel compounds were synthesized as potential drug candidates in three stages of optimization. The last stage of chemical optimization yielded two novel inhibitors for the fast-growing nonpathogenic modelMycobacterium smegmatis(Msmg).
Internal noise measures in coarse and fine motion direction discrimination tasks, and the correlation with autism traits
Authors: Orchard Edwina , Dakin Steven , van Boxtel Jeroen J.A. 
Published: February 2019

AbstractMotion perception is essential for visual guidance of behaviour and is known to be limited by both internal additive noise (arising from random fluctuations in neural activity), and by motion pooling (global integration of local motion signals across space). People with autism spectrum disorder (ASD) display abnormalities in motion processing, which has been linked to both elevated noise and abnormal pooling. However, to date, the impact of a third limit - induced internal noise (internal noise that scales up with increases is external noise) - has not been investigated in motion perception of any group. Here, we describe a new double-pass motion direction discrimination paradigm that quantifies additive noise, induced noise, and motion pooling. We measure the impact of induced noise on direction discrimination, which we ascribe to fluctuations in decision-related variables. We report that internal noise is higher individuals with high ASD traits only on coarse but not fine motion direction discrimination tasks. However, we report no significant correlations between autism traits, and additive noise, induced noise or motion pooling, in either task. We conclude that internal noise may be higher in individuals with many ASD traits, and that the assessment of induced internal noise is a useful way of exploring decision-related limits on motion perception, irrespective of ASD traits.
Diversity of Escherichia coli from the enteric microbiota in patients with Escherichia coli bacteraemia
Authors: Mosavie Mia , Blandy Oliver , Jauneikaite Elita , Caldas Isabel , Ellington Matthew J. , Woodford Neil , Sriskandan Shiranee 
Published: February 2019

ABSTRACTObjectiveThe increase in Escherichia coli bloodstream infections mandates better characterisation of the relationship between commensal and invasive isolates. This study established a simple approach to characterize diversity of E. coli in the gut reservoir from patients with either E. coli bacteraemia, other Gram-negative bacteraemia, or patients without bacteraemia not receiving antibiotics. Stool or rectal swabs from patients in the three groups were cultured on selective chromogenic agar. Genetic diversity of E. coli in gut microbiota was estimated by RAPD-PCR.ResultsEnteric samples from E. coli bacteraemia patients yielded a median of one E. coli RAPD pattern (range 1-4) compared with two (range 1-5) from groups without E. coli bacteraemia. Of relevance to large-scale clinical studies, observed diversity of E. coli among E. coli bacteraemia patients was not significantly altered by sample type (rectal swab or stool), nor by increasing the colonies tested beyond ten. Overall, hospitalised patients demonstrated an apparently limited diversity of E. coli in the enteric microbiota and this was further reduced in those with E. coli bacteraemia. The reduced diversity of E. coli within the gut during E. coli bacteraemia raises the possibility that dominant strains may outcompete other lineages in patients with bloodstream infection.
Comparative Genomics of Six Juglans Species Reveals Patterns of Disease-associated Gene Family Contractions
Authors: Trouern-Trend Alex , Falk Taylor , Zaman Sumaira , Caballero Madison , Neale David B. , Langley Charles H. , Dandekar Abhaya , Stevens Kristian A. , Wegrzyn Jill L. 
Published: February 2019

ABSTRACTJuglans (walnuts), the most speciose genus in the walnut family (Juglandaceae) represents most of the family’s commercially valuable fruit and wood-producing trees and includes several species used as rootstock in agriculture for their resistance to various abiotic and biotic stressors. We present the full structural and functional genome annotations of six Juglans species and one outgroup within Juglandaceae (Juglans regia, J. cathayensis, J. hindsii, J. microcarpa, J. nigra, J. sigillata and Pterocarya stenoptera) produced using BRAKER2 semi-unsupervised gene prediction pipeline and additional in-house developed tools. For each annotation, gene predictors were trained using 19 tissue-specific J. regia transcriptomes aligned to the genomes. Additional functional evidence and filters were applied to multiexonic and monoexonic putative genes to yield between 27,000 and 44,000 high-confidence gene models per species. Comparison of gene models to the BUSCO embryophyta dataset suggested that, on average, genome annotation completeness was 89.6%. We utilized these high quality annotations to assess gene family evolution within Juglans and among Juglans and selected Eurosid species, which revealed significant contractions in several gene families in J. hindsii including disease resistance-related Wall-associated Kinase (WAK) and Catharanthus roseus Receptor-like Kinase (CrRLK1L) and others involved in abiotic stress response. Finally, we confirmed an ancient whole genome duplication that took place in a common ancestor of Juglandaceae using site substitution comparative analysis.SIGNIFICANCEHigh-quality full genome annotations for six species of walnut (Juglans) and a wingnut (Pterocarya) outgroup were constructed using semi-unsupervised gene prediction followed by gene model filtering and functional characterization. These annotations represent the most comprehensive set for any hardwood genus to date. Comparative analyses based on the gene models uncovered rapid evolution in multiple gene families related to disease-response and a whole genome duplication in a Juglandaceae common ancestor.
Recollection and prior knowledge recruit the left angular gyrus during recognition
Authors: Bellana B. , Ladyka-Wojcik N. , Lahan S. , Moscovitch M. , Grady C. L. 
Published: February 2019

AbstractThe human angular gyrus (AG) is implicated in recollection, or our ability to retrieve detailed memory content from a specific study episode. Parallel work also highlights a key role of the AG in the representation of general knowledge and semantics. How these two lines of research converge remains unclear. The present fMRI experiment used a remember-know paradigm with famous and non-famous faces to test whether activity in the AG could be modulated by both task-specific recollection and general prior knowledge in the same participants. Increased BOLD activity in the left AG was observed during both recollection in the absence of prior knowledge (i.e., recollected > non-recollected or correctly rejected non-famous faces) and when prior knowledge was accessed in the absence of recollection (i.e., famous > non-famous correct rejections). This pattern was unique to the left AG, and was not present in any other regions of the lateral inferior parietal lobe. Furthermore, the response profile of the left AG was consistent with accounts of recollection strength. Recollection-related activity was greater for faces with longer exposures at encoding than those with shorter exposures and was greater for stimuli with prior knowledge than those without, despite prior knowledge being incidental to the recognition decision. Therefore, the left AG is recruited during the access of both task-specific recollection and general prior knowledge, with greater activity as the amount of retrieved information increases, irrespective of its episodic or semantic nature.Significance StatementThe human angular gyrus (AG) is often implicated in our ability to remember past events. A separate line of research examining our ability to represent general knowledge has also highlighted the AG as a core region of interest. To reconcile these separate views of AG function, we used fMRI to test whether the human left AG was sensitive to remembering details from a specific study episode (i.e., recollection) or more general prior knowledge, within the same participants. Overall, activity in the left AG was sensitive to both recollection and prior knowledge, suggesting any complete functional account of the left AG during retrieval must consider its sensitivity to both kinds of mnemonic representations.
Two resistance nodulation division-family efflux pumps inChromobacteriumspecies and their role in antibiotic resistance and tolerance
Authors: Benomar Saida , Evans Kara C , Unckless Robert L , Chandler Josephine R 
Published: February 2019

ABSTRACTVery little is known of the antibiotic resistance mechanisms of members of theChromobacteriumgenus. In previous studies ofChromobacterium subtsugae(formerlyC. violaceum) strain CV017, we identified a resistance nodulation division (RND)-family efflux pump (CdeAB-OprM). Here, we show thecdeAB-oprMgenes are widely distributed in members of theChromobacteriumgenus. We use antimicrobial susceptibility testing with a CV017cdeAB-oprMmutant to show the products of these genes confers resistance to a variety of antibiotics including ciprofloxacin, a clinically important antibiotic. We also identified a related RND-family pump,cseAB-oprN, in the genome of CV017 and otherC. subtsugaespecies, that is not present in other members of theChromobacteriumgenus. We demonstrate that CdeAB-OprM and CseAB-OprN are both transcriptionally induced in CV017 cells treated with sub-lethal antibiotic concentrations and they are important for induction of tolerance to different antibiotics. While CdeAB-OprM has a broad antibiotic specificity, the CseAB-OprN system is highly specific for a ribosome-targeting antibiotic produced by the saprophytic bacteriumBurkholderia thailandensis,bactobolin. Finally, we use a previously developedB. thailandensis-C. subtsugaeCV017 co-culture model to demonstrate that adding sub-lethal bactobolin at the beginning of co-culture growth increases the ability of CV017 to compete withB. thailandensisin a manner that is dependent on the CseAB-OprN system. Our results provide new information on the antibiotic resistance mechanisms ofChromobacteriumspecies and highlight the importance of efflux pumps during competition with other bacterial species.IMPORTANCEThis study describes two closely related efflux pumps in members of theChromobacteriumgenus, which includes opportunistic but often-fatal pathogens and species with highly versatile metabolic capabilities. Efflux pumps remove antibiotics from the cell and are important for antibiotic resistance. One of these pumps is broadly distributed in theChromobacteriumgenus and increases resistance to clinically relevant antibiotics. The other efflux pump is present only inChromobacterium subtsugaeand is highly specific for bactobolin, an antibiotic produced by the soil saprophyteBurkholderia thailandensis. We demonstrate these pumps can be activated to increase resistance by their antibiotic substrates, and that this activation is important forC. subtsugaeto survive in a laboratory competition experiment withB. thailandensis.These results have implications for managing antibiotic-resistantChromobacteriuminfections, bioengineering ofChromobacteriumspecies, and for understanding the evolution of efflux pumps.
EpiAlignment: alignment with both DNA sequence and epigenomic data
Authors: Lu Jia , Cao Xiaoyi , Zhong Sheng 
Published: February 2019

ABSTRACTComparative epigenomics, by subjecting both epigenome and genome to interspecies comparison, has become a powerful approach to reveal regulatory features of the genome. Thus elucidated regulatory features surpassed the information derived from comparison of genomic sequences alone. Here, we present EpiAlignment, a web-based tool to align genomic regions with both DNA sequence and epigenomic data. EpiAlignment takes DNA sequence and epigenomic profiles derived by ChIP-seq, DNase-seq, or ATAC-seq from two species as input data, and outputs the best semi-global alignments. These alignments are based on EpiAlignment scores, computed by a dynamic programming algorithm that accounts for both sequence alignment and epigenome similarity. For timely response, the EpiAlignment web server automatically initiates up to 140 computing threads depending on the size of user input data. For users’ convenience, we have pre-compiled the comparable human and mouse epigenome datasets in matched cell types and tissues from the Roadmap Epigenomics and ENCODE consortia. Users can either upload their own data or select pre-compiled datasets as inputs for EpiAlignment analyses. Results are presented in graphical and tabular formats where the entries can be interactively expanded to visualize additional features of these aligned regions. EpiAlignment is available at https://epialign.ucsd.edu/.
PathRacer: racing profile HMM paths on assembly graph
Authors: Shlemov Alexander , Korobeynikov Anton 
Published: February 2019

AbstractRecently large databases containing profile Hidden Markov Models (pHMMs) emerged. These pHMMs may represent the sequences of antibiotic resistance genes, or allelic variations amongst highly conserved housekeeping genes used for strain typing, etc. The typical application of such a database includes the alignment of contigs to pHMM hoping that the sequence of gene of interest is located within the single contig. Such a condition is often violated for metagenomes preventing the effective use of such databases.We present PathRacer — a novel standalone tool that aligns profile HMM directly to the assembly graph (performing the codon translation on fly for amino acid pHMMs). The tool provides the set of most probable paths traversed by a HMM through the whole assembly graph, regardless whether the sequence of interested is encoded on the single contig or scattered across the set of edges, therefore significantly improving the recovery of sequences of interest even from fragmented metagenome assemblies.Availabilityhttp://cab.spbu.ru/software/pathracer/
Proteins encoded by Novel ORFs have increased disorder but can be biochemically regulated and harbour pathogenic mutations
Authors: Jagannathan N. Suhas , Meena Narendra , Bhayankaram Kethaki Prathivadi , Prabakaran Sudhakaran 
Published: February 2019

AbstractRecent evidence has suggested that protein or protein-like products can be encoded by previously uncharacterized Open Reading Frames (ORFs) that we define as Novel Open Reading Frames (nORFs)1,2. These nORFs are present in both coding and non coding regions of the human genome and the novel proteins that they encode have increased the number and complexity of cellular proteome from bacteria to humans. It is a conundrum whether these protein or protein-like products could play any significant functional biological role. But hopes have been raised to target them for anticancer and antimicrobial therapy3,4. To infer whether these novel proteins can perform biological functions, we used computational predictions to systematically investigate whether their amino acid sequences can form ordered or disordered structures. Our results indicated that that these novel proteins have significantly higher predicted disorder structure compared to all known proteins, yet we do not find any correlation between the pathogenicity of the mutations and whether they are present in the ordered and disordered regions of these novel proteins. This study reveals that we should investigate these novel proteins more systematically as they may be important to understand complex diseases.
Development and validation of a next-gen health stratification engine to determine risk for multiple cardiovascular diseases
Authors: Rezaee Mehrdad , Takeh Arsia , Putrenko Igor , Ganna Andrea , Ingelsson Erik 
Published: February 2019

AbstractCardiometabolic diseases (CMD) impose greater impact on every aspect of health care than any other disease group. Accurate and in-time risk assessment of individuals for their propensity to develop CMD events is one of the most critical paths in preventing these conditions. The principal objective of the present study is to report the development, and validation of a next generation risk engine to predict CMD. UK Biobank population data was used to derive predictive models for six CMD. Missing data were imputed using imputation algorithms. Cox proportional hazard models were used to estimate annual absolute risk and relative risk of different risk factors for these conditions. In addition to conventional risk factors, the applied model included socioeconomic data, lifestyle factors and comorbidities as predictors of outcomes. In total, 416,936 individuals were included in the analysis. The derived prediction models achieved consistent and moderate-to-high discrimination performance (C-index) for all diseases: coronary artery disease (0.79), hypertension (0.82), type 2 diabetes mellitus (0.87), stroke (0.79), deep vein thrombosis (0.75), and abdominal aortic aneurysm (0.90). These results were consistent across age groups (37-73 years) and showed similar predictive abilities amongst those with pre-existing diabetes or hypertension. Calibration of risk scores showed that there was moderate overestimation of CMD-related conditions only in the highest decile of risk scores for all models. In summary, the newly developed algorithms, based on Cox proportional models, resulted in high disclination and good calibration for several CMD. The integrations of these algorithms on a single platform may have direct clinical impact.