bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating distal and proximal information to predict gene expression via a densely connected convolutional neural network
Authors: Zeng Wanwen , Wang Yong , Jiang Rui 
Published: June 2018

AbstractMotivationInteractions among such cis-regulatory elements as enhancers and promoters are main driving forces shaping context-specific chromatin structure and gene expression. Although there have been computational methods for predicting gene expression from genomic and epigenomic information, most of them overlook long-range enhancer-promoter interactions, due to the difficulty in precisely linking regulatory enhancers to target genes. Recently, a novel high-throughput experimental approach named HiChIP has been developed and generating comprehensive data on high-resolution interactions between promoters and distal enhancers. On the other hand, plenty of studies have suggested that deep learning achieves state-of-the-art performance in epigenomic signal prediction, and thus promoting the understanding of regulatory elements. In consideration of these two factors, we integrate proximal promoter sequences and HiChIP distal enhancer-promoter interactions to accurately model gene expression.ResultsWe propose DeepExpression, a densely connected convolutional neural network to predict gene expression using both promoter sequences and enhancer-promoter interactions. We demonstrate that our model consistently outperforms baseline methods not only in the classification of binary gene expression status but also in the regression of continuous gene expression levels, in both cross-validation experiments and cross-cell lines predictions. We show that sequential promoter information is more informative than experimental enhancer information while enhancer-promoter interactions are most beneficial from those within ±100 kbp around the TSS of a gene. We finally visualize motifs in both promoter and enhancer regions and show the match of identified sequence signatures and known motifs. We expect to see a wide spectrum of applications using HiChIP data in deciphering the mechanism of gene regulation.AvailabilityDeepExpression is freely available at https://github.com/wanwenzeng/DeepExpression.Contactruijiang@tsinghua.edu.cn, ywang@amss.ac.cnSupplementary informationSupplementary data are available at Bioinformatics online.
Role of DCP1-DCP2 complex regulated by viral and host microRNAs in DNA virus infection
Authors: Sun Yuechao , Zhang Xiaobo 
Published: June 2018

AbstractThe DCP1-DCP2 complex can regulate the animal antiviral immunity by the decapping of retrovirus RNAs and the suppression of RNAi pathway. However, the influence of DCP1-DCP2 complex on DNA virus infection and the regulation of DCP1-DCP2 complex by microRNAs (miRNAs) remain unclear. In this study, we investigated the role of miRNA-regulated DCP1-DCP2 complex in DNA virus infection. Our results suggested that the DCP1-DCP2 complex played a positive role in the infection of white spot syndrome virus (WSSV), a DNA virus of shrimp. The N-terminal regulatory domain of DCP2 was interacted with the EVH1 domain of DCP1, forming the DCP1-DCP2 complex. Furthermore, a host shrimp miRNA (miR-87) inhibited WSSV infection by targeting the host DCP2 gene and a viral miRNA (WSSV-miR-N46) took a negative effect on WSSV replication by targeting the host DCP1 gene. Therefore, our study provided novel insights into the underlying mechanism of DCP1-DCP2 complex and its regulation by miRNAs in virus-host interactions.The DCP1-DCP2 complex can regulate the animal antiviral immunity by the decapping of retrovirus RNAs and the suppression of RNAi pathway. In the present study, the findings indicated that the silencing of the DCP1-DCP2 complex inhibited the infection of WSSV, a DNA virus of shrimp, suggesting that the DCP1-DCP2 complex facilitated DNA virus infection. Due to the suppressive role of the DCP1-DCP2 complex in RNAi pathway against virus infection, the DCP1-DCP2 complex could promote WSSV infection in shrimp. In this context, our study contributed a novel aspect of the DCP1-DCP2 complex in virus-host interactions. Our study revealed that the host and viral miRNAs could regulate the DCP1-DCP2 complex to affect virus infection. Therefore, our study provided novel insights into the miRNA-mediated regulation of DCP1-DCP2 complex took great effects on RNAi immunity of invertebrates against virus infection.
What is the Best Available Science?: Conservation Status of Two California Desert Vertebrates
Authors: Clause Adam G. , Norment Christopher J. , Cunningham Laura , Emmerich Kevin , Buckmaster Nicholas G. , Nordin Erin , Hansen Robert W. 
Published: June 2018

AbstractScientific progress depends on evidence-based research, and reliance on accurate scholarship is essential when making management decisions for imperiled species. However, erroneous claims are sometimes perpetuated in the scientific and technical literature, which can complicate policy and regulatory judgments. The literature associated with two enigmatic California desert vertebrates, the Panamint alligator lizardElgaria panamintinaand the Inyo Mountains salamanderBatrachoseps campi, exemplifies this problem. We produced a comprehensive threat analysis and status assessment for these species, which are both under review for possible listing under the US Endangered Species Act (ESA). Despite uncertainties and limited data, we find that many sources contain factual errors about the status of these two species, particularly the original petition that advocated for ESA listing. Although localized declines may have gone undetected, no evidence exists of population declines, population extirpation, or population-scale habitat conversion forE. panamintina. However, there is evidence of recent flash flood damage to some occupiedB. campihabitat, which has possibly led to population declines at those localities. Contrary to inaccurate statements by some authors, all known populations of both species occur exclusively on federal lands, and numerous populations have likely benefited from recent federal management targeted at reducing known threats. Of the 12 threats that we identified for one or both species, only three currently appear to be serious: water diversions, climate change, and flash floods. The remaining threats are neither widespread nor severe, despite numerous contrary yet poorly supported statements in the literature. We thus evaluate the contemporary conservation status of both species as relatively secure, althoughB. campiis more at-risk compared toE. panamintina. This conclusion is independently supported by a recent review. Nonetheless, ongoing stewardship of these species in a multi-use context by federal agencies remains vital, and we identify several priority management actions and research needs for both species. We also recommend updated determinations on the IUCN Red List, and the Species of Conservation Concern list of the Inyo National Forest. To maximize the quality and effectiveness of conservation planning, we urge government agencies, non-governmental organizations, and individual scientists to maintain high standards of scholarship and decision-making.
Structure simulation of thrombopoietin receptor C-MPL with missense SNPs and its geographical distribution
Authors: Zheng Weizhong , Zeng Dongyu , Zhou Qi , Li Zhilan , Liang Haojian 
Published: June 2018

AbstractMpl is a key gene controlling the process of proliferation and differentiation of megakaryocyte and several studies reported that the mutation of mpl will even cause accurate megakaryocyte leukemia. By overlapping the missense mutation in NCBI and recorded SNP in 1000 genome database, we sorted out 4 SNPs(rs190983971, rs563996763, rs546510242, rs373621350) to find out its conformational changes. With Phyre v2.0, we simulated the secondary and tertiary structure change caused by the SNP and compared it with the original structure. The significant changes indicated its potential in leading to diseases associated with platelet reproduction. Finally, according to 1000 genome database, we constructed the geographically distribution of different populations and its SNPs carrying rate.
Novel Significant Stage-Specific Differentially Expressed Genes in Liver Hepatocellular Carcinoma
Authors: Sarathi Arjun , Palaniappan Ashok 
Published: June 2018

ABSTRACTLiver cancer is among the top deadly cancers worldwide with a very poor prognosis, and the liver is a particularly vulnerable site for metastasis of other cancers. In this study, we developed a novel computational framework for the stage-specific analysis of hepatocellular carcinoma initiation and progression. Using publicly available clinical and RNA-Seq data of cancer samples and controls, we annotated the gene expression matrix with sample stages. We performed a linear modelling analysis of gene expression across all stages and found significant genome-wide changes in gene expression in cancer samples relative to control. Using a contrast against the control, we were able to identify differentially expressed genes (log fold change >2) that were significant at an adjusted p-value < 10E-3. In order to identify genes that were specific to each stage without confounding differential expression in other stages, we developed a full set of pairwise stage contrasts and enforced a p-value threshold (<0.05) for each such contrast. Genes were specific for a stage if they passed all the significance filters for that stage. Our analysis yielded two stage-I specific genes (CA9, WNT7B), two stage-II specific genes (APOBEC3B, FAM186A), ten stage-III specific genes including DLG5, PARI and GNMT, and ten stage-IV specific genes including GABRD, PGAM2 and PECAM1. Of these, only APOBEC3B is an established cancer driver gene. DLG5 was found to be tumor-promoting contrary to the cancer literature on this gene. Further, GABRD, well studied in literature on other cancers, emerged as a stage-IV specific gene. Our findings could be validated using multiple sources of omics data as well as experimentally. The biomarkers identified herein could potentially underpin diagnosis as well as pinpoint drug targets.
Long-range chromatin interactions on the inactive X and atHoxclusters are regulated by the non-canonical SMC protein Smchd1
Authors: Jansz Natasha , Keniry Andrew , Trussart Marie , Bildsoe Heidi , Beck Tamara , Tonks Ian D. , Mould Arne W. , Hickey Peter , Breslin Kelsey , Iminitoff Megan , Ritchie Matthew E. , McGlinn Edwina , Kay Graham F. , Murphy James M. , Blewitt Marnie E. 
Published: June 2018

AbstractThe regulation of higher order chromatin structure is complex and dynamic; however we do not yet understand the full suite of mechanisms governing architecture. Here we reveal the non-canonical SMC protein Smchd1 as a novel regulator of long-range chromatin interactions, and add it to the canon of epigenetic proteins required forHoxgene regulation. The effect of losing Smchd1-dependent chromatin interactions has varying outcomes dependent on chromatin context. At autosomal targets transcriptionally sensitive to Smchd1 deletion, we find increased short-range interactions and ectopic enhancer activation. By contrast, the inactive X chromosome is transcriptionally refractive to Smchd1 ablation, despite chromosome-wide increases in short-range interactions. There we observe spreading of H3K27me3 domains into regions not normally decorated by this mark. Together these data suggest Smchd1 has the capacity to insulate the chromatin, thereby limiting access to other chromatin modifying proteins.
Functional Role of Annexins in Zebrafish Caudal Fin Regeneration – A Gene Knockdown Approach in Regenerating Tissue
Authors: Quoseena Mir , Vuppaladadium Sowmya , Hussain Shahid , Bharathi Swarna , Idris Mohammed M 
Published: June 2018

AbstractRegeneration is an adaptive phenomenon with wide biological implications spread heterogeneously in almost all the organism including human beings. The ability of regeneration varies from species to species for its impediment. Epimorphic regeneration of zebrafish caudal fin tissue is most widely studied regeneration mechanism for its discrete and rapid regenerative capability. Several genes/proteins were found to be associated with zebrafish caudal fin tissue regeneration. Here, we have evaluated the functional role ofAnnexin 2aand2bgenes in adult zebrafish caudal fin tissue undergoing regeneration using a novel CRSISPR-Cas9 gene knock down approach. Knock down of both the genes individually elicited in decelerated regeneration and down regulation of target genes and its partner genes/proteins such as ANXA1a, ANXA5b and ANXA13. This study validates a novel gene targeting approach and the possible role of annexin in regeneration mechanism.
On identifying collective displacements in apo-proteins that reveal eventual binding pathways
Authors: Prakashchand Dube Dheeraj , Ahalawat Navjeet , Khandelia Himanshu , Mondal Jagannath , Sengupta Surajit 
Published: June 2018

AbstractBinding of small molecules to proteins often involves large conformational changes in the latter, which open up pathways to the binding site. Observing and pinpointing these rare events in large scale, all-atom, computations of specific protein-ligand complexes, is expensive and to a great extent serendipitous. Further, relevant collective variables which characterise specific binding or un-binding scenarios are still difficult to identify despite the large body of work on the subject. Here, we show that possible primary and secondary binding pathways can be discovered from short simulations of the apo-protein without waiting for an actual binding event to occur. We use a projection formalism, introduced earlier to study deformation in solids, to analyse local atomic displacements into two mutually orthogonal subspaces — those which are “affine” i.e. expressible as a homogeneous deformation of the native structure, and those which are not. The susceptibility to non-affine displacements among the various residues in the apo-protein is then shown to correlate with typical binding pathways and sites crucial for allosteric modifications. We validate our observation with all-atom computations of three proteins, T4-Lysozyme, Src kinase and Cytochrome P450.
A synthetic system that senses Candida albicans and inhibits virulence factors
Authors: Tscherner Michael , Giessen Tobias W. , Markey Laura , Kumamoto Carol A. , Silver Pamela A. 
Published: June 2018

AbstractDue to a limited set of antifungals available and problems in early diagnosis invasive fungal infections caused by Candida species are among the most common hospital-acquired infections with staggering mortality rates. Here, we describe an engineered system able to sense and respond to the fungal pathogen Candida albicans, the most common cause of candidemia. In doing so, we identified hydroxyphenylacetic acid (HPA) as a novel molecule secreted by C. albicans. Furthermore, we engineered E. coli to be able to sense HPA produced by C. albicans. Finally, we constructed a sense-and-respond system by coupling the C. albicans sensor to the production of an inhibitor of hypha formation thereby reducing filamentation, virulence factor expression and fungal-induced epithelial damage. This system could be used as a basis for the development of novel prophylactic approaches to prevent fungal infections.
Storage of prescription veterinary medicines on UK dairy farms: a cross-sectional study
Authors: Rees Gwen M. , Barrett David C. , Buller Henry J. , Mills Harriet L. , Reyher Kristen K. 
Published: June 2018

AbstractPrescription veterinary medicine (PVM) use in the United Kingdom is an area of increasing focus for the veterinary profession. While many studies measure antimicrobial use on dairy farms, none report the quantity of antimicrobials stored on farms, nor the ways in which they are stored. The majority of PVM treatments occur in the absence of the prescribing veterinarian, yet there is an identifiable knowledge gap surrounding PVM use and farmer decision making. To provide an evidence base for future work on PVM use, data were collected from 27 dairy farms in England and Wales in Autumn 2016. The number of different PVM stored on farms ranged from 9-35, with antimicrobials being the most common therapeutic group stored. Injectable antimicrobials comprised the greatest weight of active ingredient found while intramammary antimicrobials were the most frequent unit of medicine stored. Antimicrobials classed by the European Medicines Agency as critically-important to human health were present on most farms, and the presence of expired medicines and medicines not licensed for use in dairy cattle was also common. The medicine resources available to farmers are likely to influence their treatment decisions, therefore evidence of the PVM stored on farms can help inform understanding of medicine use.
CRISPR/Cas9-mediated gene knockin in the hydroid Hydractinia symbiolongicarpus
Authors: Sanders Steven M. , Ma Zhiwei , Hughes Julia M. , Riscoe Brooke M. , Gibson Gregory A. , Watson Alan M. , Flici Hakima , Frank Uri , Schnitzler Christine E. , Baxevanis Andreas D. , Nicotra Matthew L. 
Published: June 2018

AbstractBackgroundHydractinia symbiolongicarpus, a colonial cnidarian, is a tractable model system for many cnidarian-specific and general biological questions. Until recently, tests of gene function in Hydractinia have relied on laborious forward genetic approaches, randomly integrated transgenes, or transient knockdown of mRNAs.ResultsHere, we report the use of CRISPR/Cas9 genome editing to generate targeted genomic insertions in H. symbiolonigcarpus. We used CRISPR/Cas9 to promote homologous recombination of two fluorescent reporters, eGFP and tdTomato, into the Eukaryotic elongation factor 1 alpha (Eef1a) locus. We demonstrate that the transgenes are expressed ubiquitously and are stable over two generations of breeding. We further demonstrate that CRISPR/Cas9 genome editing can be used to mark endogenous proteins with FLAG or StrepII-FLAG affinity tags to enable in vivo and ex vivo protein studies.ConclusionsThis is the first account of CRISPR/Cas9 mediated knockins in Hydractinia and the first example of the germline transmission of a CRISPR/Cas9 inserted transgene in a cnidarian. The ability to precisely insert exogenous DNA into the Hydractinia genome will enable sophisticated genetic studies and further development of functional genomics tools in this understudied cnidarian model.
Machine learning techniques for classifying the mutagenic origins of point mutations
Authors: Zhu Yicheng , Ong Cheng Soon , Huttley Gavin A 
Published: June 2018

AbstractThere is increasing interest in developing diagnostics that discriminate individual mutagenic mechanisms in a range of applications that include identifying population specific mutagenesis and resolving distinct mutation signatures in cancer samples. Analyses for these applications assume that mutagenic mechanisms have a unique relationship with neighboring bases that allows them to be distinguished. Direct support for this assumption is limited to a small number of simple cases, e.g. CpG hypermutability. We have directly evaluated whether the mechanistic origin of a point mutation can be resolved using only sequence context for a more complicated case. We contrasted mutations originating from the multitude of mutagenic processes that normally operate in the mouse germline with those induced by the potent mutagen N-ethyl-N-nitrosourea (ENU). The considerable overlap in the mutation spectra of these two samples make this a challenging problem. Employing a new, robust log-linear modeling method, we demonstrate that neighboring bases contain information regarding point mutation direction that differs between the ENU-induced and spontaneous mutation classes. A logistic regression classifier proved to be substantially more powerful at discriminating between the different mutation classes than alternatives. Concordance between the feature set of the best classifier and information content analyses suggest our results can be generalized to other mutation classification problems. We conclude that machine learning can be used to build a practical classification tool to identify the mutation mechanism for individual genetic variants. Software implementing our approach is freely available under the BSD 3-clause license.
Unbiased Precision Estimation under Separate Sampling
Authors: Xie Shuilian , Braga-Neto Ulisses M. 
Published: June 2018

AbstractMotivationPrecision and recall have become very popular classification accuracy metrics in the statistical learning literature. These metrics are ordinarily defined under the assumption that the data are sampled randomly from the mixture of the populations. However, observational case-control studies for biomarker discovery often collect data that are sampled separately from the case and control populations, particularly in the case of rare diseases. This discrepancy may introduce severe bias in classifier accuracy estimation.ResultsWe demonstrate, using both analytical and numerical methods, that classifier precision estimates can display strong bias under separating sampling, with the bias magnitude depending on the difference between the case prevalences in the data and in the actual population. We show that this bias is systematic in the sense that it cannot be reduced by increasing sample size. If information about the true case prevalence is available from public health records, then a modified precision estimator is proposed that displays smaller bias, which can in fact be reduced to zero as sample size increases under regularity conditions on the classification algorithm. The accuracy of the theoretical analysis and the performance of the proposed precision estimator under separate sampling are investigated using synthetic and real data from observational case-control studies. The results confirmed that the proposed precision estimator indeed becomes unbiased as sample size increases, while the ordinary precision estimator may display large bias, particularly in the case of rare diseases.AvailabilityExtra plots are available as Supplementary Materials.Author summaryBiomedical data are often sampled separately from the case and control populations, particularly in the case of rare diseases. Precision is a popular classification accuracy metric in the statistical learning literature, which implicitly assumes that the data are sampled randomly from the mixture of the populations. In this paper we study the bias of precision under separate sampling using theoretical and numerical methods. We also propose a precision estimator for separate sampling in the case when the prevalence is known from public health records. The results confirmed that the proposed precision estimator becomes unbiased as sample size increases, while the ordinary precision estimator may display large bias, particularly in the case of rare diseases. In the absence of any knowledge about disease prevalence, precision estimates should be avoided under separate sampling.