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    1104 results match your criteria Briefings in bioinformatics[Journal]

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    Network approaches to systems biology analysis of complex disease: integrative methods for multi-omics data.
    Brief Bioinform 2017 Jun 30. Epub 2017 Jun 30.
    In the past decade, significant progress has been made in complex disease research across multiple omics layers from genome, transcriptome and proteome to metabolome. There is an increasing awareness of the importance of biological interconnections, and much success has been achieved using systems biology approaches. However, because of the typical focus on one single omics layer at a time, existing systems biology findings explain only a modest portion of complex disease. Read More

    Alignment-free inference of hierarchical and reticulate phylogenomic relationships.
    Brief Bioinform 2017 Jun 30. Epub 2017 Jun 30.
    We are amidst an ongoing flood of sequence data arising from the application of high-throughput technologies, and a concomitant fundamental revision in our understanding of how genomes evolve individually and within the biosphere. Workflows for phylogenomic inference must accommodate data that are not only much larger than before, but often more error prone and perhaps misassembled, or not assembled in the first place. Moreover, genomes of microbes, viruses and plasmids evolve not only by tree-like descent with modification but also by incorporating stretches of exogenous DNA. Read More

    Nanopore sequencing data analysis: state of the art, applications and challenges.
    Brief Bioinform 2017 Jun 16. Epub 2017 Jun 16.
    The nanopore sequencing process is based on the transit of a DNA molecule through a nanoscopic pore, and since the 90s is considered as one of the most promising approaches to detect polymeric molecules. In 2014, Oxford Nanopore Technologies (ONT) launched a beta-testing program that supplied the scientific community with the first prototype of a nanopore sequencer: the MinION. Thanks to this program, several research groups had the opportunity to evaluate the performance of this novel instrument and develop novel computational approaches for analyzing this new generation of data. Read More

    Biomedical text mining for research rigor and integrity: tasks, challenges, directions.
    Brief Bioinform 2017 Jun 13. Epub 2017 Jun 13.
    An estimated quarter of a trillion US dollars is invested in the biomedical research enterprise annually. There is growing alarm that a significant portion of this investment is wasted because of problems in reproducibility of research findings and in the rigor and integrity of research conduct and reporting. Recent years have seen a flurry of activities focusing on standardization and guideline development to enhance the reproducibility and rigor of biomedical research. Read More

    Investigating microRNA-mediated regulation of the nascent nuclear transcripts in plants: a bioinformatics workflow.
    Brief Bioinform 2017 Jun 14. Epub 2017 Jun 14.
    Most of the microRNAs (miRNAs) play their regulatory roles through posttranscriptional target decay or translational inhibition. For both plants and animals, these regulatory events were previously considered to take place in cytoplasm, as mature miRNAs were observed to be exported to the cytoplasm for Argonaute (AGO) loading and subsequent target binding. Recently, this notion was challenged by increasing pieces of evidence in the animal cells that uncovered the nuclear importation and action of the AGO-associated miRNAs. Read More

    Recent computational developments on CLIP-seq data analysis and microRNA targeting implications.
    Brief Bioinform 2017 Jun 12. Epub 2017 Jun 12.
    Cross-Linking Immunoprecipitation associated to high-throughput sequencing (CLIP-seq) is a technique used to identify RNA directly bound to RNA-binding proteins across the entire transcriptome in cell or tissue samples. Recent technological and computational advances permit the analysis of many CLIP-seq samples simultaneously, allowing us to reveal the comprehensive network of RNA-protein interaction and to integrate it to other genome-wide analyses. Therefore, the design and quality management of the CLIP-seq analyses are of critical importance to extract clean and biological meaningful information from CLIP-seq experiments. Read More

    Power and sample size calculations for high-throughput sequencing-based experiments.
    Brief Bioinform 2017 Jun 9. Epub 2017 Jun 9.
    Power/sample size (power) analysis estimates the likelihood of successfully finding the statistical significance in a data set. There has been a growing recognition of the importance of power analysis in the proper design of experiments. Power analysis is complex, yet necessary for the success of large studies. Read More

    The genetic architecture of heterochronsy as a quantitative trait: lessons from a computational model.
    Brief Bioinform 2017 May 30. Epub 2017 May 30.
    Heterochrony is known as a developmental change in the timing or rate of ontogenetic events across phylogenetic lineages. It is a key concept synthesizing development into ecology and evolution to explore the mechanisms of how developmental processes impact on phenotypic novelties. A number of molecular experiments using contrasting organisms in developmental timing have identified specific genes involved in heterochronic variation. Read More

    Dynamic-BM: multispecies Dynamic BodyMap database from temporal RNA-seq data.
    Brief Bioinform 2017 Jun 1. Epub 2017 Jun 1.
    Biological processes, especially developmental processes, are often dynamic. Previous BodyMap projects for human and mouse have provided researchers with portals to tissue-specific gene expression, but these efforts have not included dynamic gene expression patterns. Over the past few years, substantial progress in our understanding of the molecular mechanisms of protein-coding and long noncoding RNA (lncRNA) genes in development processes has been achieved through numerous time series RNA sequencing (RNA-seq) studies. Read More

    A comprehensive evaluation of popular proteomics software workflows for label-free proteome quantification and imputation.
    Brief Bioinform 2017 May 31. Epub 2017 May 31.
    Label-free mass spectrometry (MS) has developed into an important tool applied in various fields of biological and life sciences. Several software exist to process the raw MS data into quantified protein abundances, including open source and commercial solutions. Each software includes a set of unique algorithms for different tasks of the MS data processing workflow. Read More

    ceRNAs in plants: computational approaches and associated challenges for target mimic research.
    Brief Bioinform 2017 May 30. Epub 2017 May 30.
    The competing endogenous RNA hypothesis has gained increasing attention as a potential global regulatory mechanism of microRNAs (miRNAs), and as a powerful tool to predict the function of many noncoding RNAs, including miRNAs themselves. Most studies have been focused on animals, although target mimic (TMs) discovery as well as important computational and experimental advances has been developed in plants over the past decade. Thus, our contribution summarizes recent progresses in computational approaches for research of miRNA:TM interactions. Read More

    Seeing the wood for the trees: a forest of methods for optimization and omic-network integration in metabolic modelling.
    Brief Bioinform 2017 May 30. Epub 2017 May 30.
    Metabolic modelling has entered a mature phase with dozens of methods and software implementations available to the practitioner and the theoretician. It is not easy for a modeller to be able to see the wood (or the forest) for the trees. Driven by this analogy, we here present a 'forest' of principal methods used for constraint-based modelling in systems biology. Read More

    Optimizing drug development in oncology by clinical trial simulation: Why and how?
    Brief Bioinform 2017 May 29. Epub 2017 May 29.
    In therapeutic research, the safety and efficacy of pharmaceutical products are necessarily tested on humans via clinical trials after an extensive and expensive preclinical development period. Methodologies such as computer modeling and clinical trial simulation (CTS) might represent a valuable option to reduce animal and human assays. The relevance of these methods is well recognized in pharmacokinetics and pharmacodynamics from the preclinical phase to postmarketing. Read More

    Bioinformatic analysis of bacteria and host cell dual RNA-sequencing experiments.
    Brief Bioinform 2017 May 23. Epub 2017 May 23.
    Bacterial pathogens subvert host cells by manipulating cellular pathways for survival and replication; in turn, host cells respond to the invading pathogen through cascading changes in gene expression. Deciphering these complex temporal and spatial dynamics to identify novel bacterial virulence factors or host response pathways is crucial for improved diagnostics and therapeutics. Dual RNA sequencing (dRNA-Seq) has recently been developed to simultaneously capture host and bacterial transcriptomes from an infected cell. Read More

    Genome-wide discovery of viral microRNAs based on phylogenetic analysis and structural evolution of various human papillomavirus subtypes.
    Brief Bioinform 2017 May 20. Epub 2017 May 20.
    In mammals, microRNAs (miRNAs) play key roles in controlling posttranscriptional regulation through binding to the mRNAs of target genes. Recently, it was discovered that viral miRNAs may be involved in human cancers and diseases. It is likely that viral miRNAs help viruses enter the latent phase of their life cycle and become undetected by the host's immune system, while increasing the host's risk for cancer development. Read More

    Large-scale data-driven integrative framework for extracting essential targets and processes from disease-associated gene data sets.
    Brief Bioinform 2017 May 18. Epub 2017 May 18.
    Populations worldwide currently face several public health challenges, including growing prevalence of infections and the emergence of new pathogenic organisms. The cost and risk associated with drug development make the development of new drugs for several diseases, especially orphan or rare diseases, unappealing to the pharmaceutical industry. Proof of drug safety and efficacy is required before market approval, and rigorous testing makes the drug development process slow, expensive and frequently result in failure. Read More

    Mutational signatures and mutable motifs in cancer genomes.
    Brief Bioinform 2017 May 11. Epub 2017 May 11.
    Cancer is a genetic disorder, meaning that a plethora of different mutations, whether somatic or germ line, underlie the etiology of the 'Emperor of Maladies'. Point mutations, chromosomal rearrangements and copy number changes, whether they have occurred spontaneously in predisposed individuals or have been induced by intrinsic or extrinsic (environmental) mutagens, lead to the activation of oncogenes and inactivation of tumor suppressor genes, thereby promoting malignancy. This scenario has now been recognized and experimentally confirmed in a wide range of different contexts. Read More

    Deep learning for healthcare: review, opportunities and challenges.
    Brief Bioinform 2017 May 6. Epub 2017 May 6.
    Gaining knowledge and actionable insights from complex, high-dimensional and heterogeneous biomedical data remains a key challenge in transforming health care. Various types of data have been emerging in modern biomedical research, including electronic health records, imaging, -omics, sensor data and text, which are complex, heterogeneous, poorly annotated and generally unstructured. Traditional data mining and statistical learning approaches typically need to first perform feature engineering to obtain effective and more robust features from those data, and then build prediction or clustering models on top of them. Read More

    Bioinformatics tools for quantitative and functional metagenome and metatranscriptome data analysis in microbes.
    Brief Bioinform 2017 May 8. Epub 2017 May 8.
    Metagenomic and metatranscriptomic sequencing approaches are more frequently being used to link microbiota to important diseases and ecological changes. Many analyses have been used to compare the taxonomic and functional profiles of microbiota across habitats or individuals. While a large portion of metagenomic analyses focus on species-level profiling, some studies use strain-level metagenomic analyses to investigate the relationship between specific strains and certain circumstances. Read More

    Advances in computational approaches in identifying synergistic drug combinations.
    Brief Bioinform 2017 May 5. Epub 2017 May 5.
    Accumulated empirical clinical experience, supported by animal or cell line models, has initiated efforts of predicting synergistic combinatorial drugs with more-than-additive effect compared with the sum of the individual agents. Aiming to construct better computational models, this review started from the latest updated data resources of combinatorial drugs, then summarized the reported mechanism of the known synergistic combinations from aspects of drug molecular and pharmacological patterns, target network properties and compound functional annotation. Based on above, we focused on the main in silico strategies recently published, covering methods of molecular modeling, mathematical simulation, optimization of combinatorial targets and pattern-based statistical/learning model. Read More

    In silico polypharmacology of natural products.
    Brief Bioinform 2017 Apr 27. Epub 2017 Apr 27.
    Natural products with polypharmacological profiles have demonstrated promise as novel therapeutics for various complex diseases, including cancer. Currently, many gaps exist in our knowledge of which compounds interact with which targets, and experimentally testing all possible interactions is infeasible. Recent advances and developments of systems pharmacology and computational (in silico) approaches provide powerful tools for exploring the polypharmacological profiles of natural products. Read More

    Pioneering topological methods for network-based drug-target prediction by exploiting a brain-network self-organization theory.
    Brief Bioinform 2017 Apr 26. Epub 2017 Apr 26.
    The bipartite network representation of the drug-target interactions (DTIs) in a biosystem enhances understanding of the drugs' multifaceted action modes, suggests therapeutic switching for approved drugs and unveils possible side effects. As experimental testing of DTIs is costly and time-consuming, computational predictors are of great aid. Here, for the first time, state-of-the-art DTI supervised predictors custom-made in network biology were compared-using standard and innovative validation frameworks-with unsupervised pure topological-based models designed for general-purpose link prediction in bipartite networks. Read More

    Long noncoding RNA: a crosslink in biological regulatory network.
    Brief Bioinform 2017 Apr 24. Epub 2017 Apr 24.
    Long noncoding RNAs (lncRNAs) had been defined as a novel class of functional RNAs longer than 200 nucleotides around a decade ago. It is widely acknowledged that lncRNAs play a significant role in regulation of gene expression, but the biological and molecular mechanisms are diverse and complex, and remain to be determined. Especially, the regulatory network of lncRNAs associated with other biological molecules is still a controversial matter, thus becoming a new frontier of the studies on transcriptome. Read More

    Dynamic modeling and network approaches for omics time course data: overview of computational approaches and applications.
    Brief Bioinform 2017 Apr 18. Epub 2017 Apr 18.
    Inferring networks and dynamics of genes, proteins, cells and other biological entities from high-throughput biological omics data is a central and challenging issue in computational and systems biology. This is essential for understanding the complexity of human health, disease susceptibility and pathogenesis for Predictive, Preventive, Personalized and Participatory (P4) system and precision medicine. The delineation of the possible interactions of all genes/proteins in a genome/proteome is a task for which conventional experimental techniques are ill suited. Read More

    Improving data workflow systems with cloud services and use of open data for bioinformatics research.
    Brief Bioinform 2017 Apr 16. Epub 2017 Apr 16.
    Data workflow systems (DWFSs) enable bioinformatics researchers to combine components for data access and data analytics, and to share the final data analytics approach with their collaborators. Increasingly, such systems have to cope with large-scale data, such as full genomes (about 200 GB each), public fact repositories (about 100 TB of data) and 3D imaging data at even larger scales. As moving the data becomes cumbersome, the DWFS needs to embed its processes into a cloud infrastructure, where the data are already hosted. Read More

    Comparative analysis of de novo assemblers for variation discovery in personal genomes.
    Brief Bioinform 2017 Apr 11. Epub 2017 Apr 11.
    Current variant discovery approaches often rely on an initial read mapping to the reference sequence. Their effectiveness is limited by the presence of gaps, potential misassemblies, regions of duplicates with a high-sequence similarity and regions of high-sequence divergence in the reference. Also, mapping-based approaches are less sensitive to large INDELs and complex variations and provide little phase information in personal genomes. Read More

    Bioinformatics tools for the identification of gene clusters that biosynthesize specialized metabolites.
    Brief Bioinform 2017 Apr 7. Epub 2017 Apr 7.
    Specialized metabolites (also called natural products or secondary metabolites) derived from bacteria, fungi, marine organisms and plants constitute an important source of antibiotics, anti-cancer agents, insecticides, immunosuppressants and herbicides. Many specialized metabolites in bacteria and fungi are biosynthesized via metabolic pathways whose enzymes are encoded by clustered genes on a chromosome. Metabolic gene clusters comprise a group of physically co-localized genes that together encode enzymes for the biosynthesis of a specific metabolite. Read More

    The anatomy of phenotype ontologies: principles, properties and applications.
    Brief Bioinform 2017 Apr 6. Epub 2017 Apr 6.
    The past decade has seen an explosion in the collection of genotype data in domains as diverse as medicine, ecology, livestock and plant breeding. Along with this comes the challenge of dealing with the related phenotype data, which is not only large but also highly multidimensional. Computational analysis of phenotypes has therefore become critical for our ability to understand the biological meaning of genomic data in the biological sciences. Read More

    CASH: a constructing comprehensive splice site method for detecting alternative splicing events.
    Brief Bioinform 2017 Apr 6. Epub 2017 Apr 6.
    RNA-sequencing (RNA-seq) can generate millions of reads to provide clues for analyzing novel or abnormal alternative splicing (AS) events in cells. However, current methods for exploring AS events are still far from being satisfactory. Here, we present Comprehensive AS Hunting (CASH), which constructs comprehensive splice sites including known and novel AS sites in cells, and identifies differentially AS events between cells. Read More

    Experimental design and data analysis of Ago-RIP-Seq experiments for the identification of microRNA targets.
    Brief Bioinform 2017 03 31. Epub 2017 Mar 31.
    The identification of microRNA (miRNA) target genes is crucial for understanding miRNA function. Many methods for the genome-wide miRNA target identification have been developed in recent years; however, they have several limitations including the dependence on low-confident prediction programs and artificial miRNA manipulations. Ago-RNA immunoprecipitation combined with high-throughput sequencing (Ago-RIP-Seq) is a promising alternative. Read More

    Evaluating de novo sequencing in proteomics: already an accurate alternative to database-driven peptide identification?
    Brief Bioinform 2017 Mar 21. Epub 2017 Mar 21.
    While peptide identifications in mass spectrometry (MS)-based shotgun proteomics are mostly obtained using database search methods, high-resolution spectrum data from modern MS instruments nowadays offer the prospect of improving the performance of computational de novo peptide sequencing. The major benefit of de novo sequencing is that it does not require a reference database to deduce full-length or partial tag-based peptide sequences directly from experimental tandem mass spectrometry spectra. Although various algorithms have been developed for automated de novo sequencing, the prediction accuracy of proposed solutions has been rarely evaluated in independent benchmarking studies. Read More

    Row versus column correlations: avoiding the ecological fallacy in RNA/protein expression studies.
    Brief Bioinform 2017 Mar 26. Epub 2017 Mar 26.
    Biomedical researchers are often interested in computing the correlation between RNA and protein abundance. However, correlations can be computed between rows of a data matrix or between columns, and the results are not the same. The belief that these two types of correlation are estimating the same phenomenon is a special case of a well-known logical error called the ecological fallacy. Read More

    Identification of differentially expressed peptides in high-throughput proteomics data.
    Brief Bioinform 2017 Mar 23. Epub 2017 Mar 23.
    With the advent of high-throughput proteomics, the type and amount of data pose a significant challenge to statistical approaches used to validate current quantitative analysis. Whereas many studies focus on the analysis at the protein level, the analysis of peptide-level data provides insight into changes at the sub-protein level, including splice variants, isoforms and a range of post-translational modifications. Statistical evaluation of liquid chromatography-mass spectrometry/mass spectrometry peptide-based label-free differential data is most commonly performed using a t-test or analysis of variance, often after the application of data imputation to reduce the number of missing values. Read More

    Context-based retrieval of functional modules in protein-protein interaction networks.
    Brief Bioinform 2017 Mar 27. Epub 2017 Mar 27.
    Various techniques have been developed for identifying the most probable interactants of a protein under a given biological context. In this article, we dissect the effects of the choice of the protein-protein interaction network (PPI) and the manipulation of PPI settings on the network neighborhood of the influenza A virus (IAV) network, as well as hits in genome-wide small interfering RNA screen results for IAV host factors. We investigate the potential of context filtering, which uses text mining evidence linked to PPI edges, as a complement to the edge confidence scores typically provided in PPIs for filtering, for obtaining more biologically relevant network neighborhoods. Read More

    Comprehensive assessment of flexible-ligand docking algorithms: current effectiveness and challenges.
    Brief Bioinform 2017 Mar 14. Epub 2017 Mar 14.
    Protein-ligand docking has been playing an important role in modern drug discovery. To model drug-target binding in real systems, a number of flexible-ligand docking algorithms with different sampling strategies and scoring methods have been subsequently developed over the past three decades, while rigid-ligand docking is still being used because of its compelling computational efficiency. Here, a comprehensive assessment has been conducted to investigate the effectiveness of flexible-ligand docking versus rigid-ligand docking for three representative docking algorithms (global optimization, incremental construction and multi-conformer docking) in virtual screening and pose prediction on the Directory of Useful Decoys. Read More

    GWAS summary-based pathway analysis correcting for the genetic confounding impact of environmental exposures.
    Brief Bioinform 2017 Mar 8. Epub 2017 Mar 8.
    Genome-wide association study (GWAS)-based pathway association analysis is a powerful approach for the genetic studies of human complex diseases. However, the genetic confounding effects of environment exposure-related genes can decrease the accuracy of GWAS-based pathway association analysis of target diseases. In this study, we developed a pathway association analysis approach, named Mendelian randomization-based pathway enrichment analysis (MRPEA), which was capable of correcting the genetic confounding effects of environmental exposures, using the GWAS summary data of environmental exposures. Read More

    An algorithmic perspective of de novo cis-regulatory motif finding based on ChIP-seq data.
    Brief Bioinform 2017 Mar 8. Epub 2017 Mar 8.
    Transcription factors are proteins that bind to specific DNA sequences and play important roles in controlling the expression levels of their target genes. Hence, prediction of transcription factor binding sites (TFBSs) provides a solid foundation for inferring gene regulatory mechanisms and building regulatory networks for a genome. Chromatin immunoprecipitation sequencing (ChIP-seq) technology can generate large-scale experimental data for such protein-DNA interactions, providing an unprecedented opportunity to identify TFBSs (a. Read More

    Review and comparative assessment of sequence-based predictors of protein-binding residues.
    Brief Bioinform 2017 Mar 1. Epub 2017 Mar 1.
    Understanding of molecular mechanisms that govern protein-protein interactions and accurate modeling of protein-protein docking rely on accurate identification and prediction of protein-binding partners and protein-binding residues. We review over 40 methods that predict protein-protein interactions from protein sequences including methods that predict interacting protein pairs, protein-binding residues for a pair of interacting sequences and protein-binding residues in a single protein chain. We focus on the latter methods that provide residue-level annotations and that can be broadly applied to all protein sequences. Read More

    Comparison of the general co-expression landscapes between human and mouse.
    Brief Bioinform 2017 Mar 14. Epub 2017 Mar 14.
    The murine model serves as an important experimental system in biomedical science because of its high degree of similarities at the sequence level with human. Recent studies have compared the transcriptional landscapes between human and mouse, but the general co-expression landscapes have not been characterized. Here, we calculated the general co-expression coefficients and constructed the general co-expression maps for human and mouse. Read More

    A survey of the approaches for identifying differential methylation using bisulfite sequencing data.
    Brief Bioinform 2017 Mar 8. Epub 2017 Mar 8.
    DNA methylation is an important epigenetic mechanism that plays a crucial role in cellular regulatory systems. Recent advancements in sequencing technologies now enable us to generate high-throughput methylation data and to measure methylation up to single-base resolution. This wealth of data does not come without challenges, and one of the key challenges in DNA methylation studies is to identify the significant differences in the methylation levels of the base pairs across distinct biological conditions. Read More

    Selecting between-sample RNA-Seq normalization methods from the perspective of their assumptions.
    Brief Bioinform 2017 Feb 27. Epub 2017 Feb 27.
    RNA-Seq is a widely used method for studying the behavior of genes under different biological conditions. An essential step in an RNA-Seq study is normalization, in which raw data are adjusted to account for factors that prevent direct comparison of expression measures. Errors in normalization can have a significant impact on downstream analysis, such as inflated false positives in differential expression analysis. Read More

    Critical evaluation of bioinformatics tools for the prediction of protein crystallization propensity.
    Brief Bioinform 2017 Feb 27. Epub 2017 Feb 27.
    X-ray crystallography is the main tool for structural determination of proteins. Yet, the underlying crystallization process is costly, has a high attrition rate and involves a series of trial-and-error attempts to obtain diffraction-quality crystals. The Structural Genomics Consortium aims to systematically solve representative structures of major protein-fold classes using primarily high-throughput X-ray crystallography. Read More

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