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In the tourism industry, the sales of local specialties is an important part, and the package design and integrity of the specialties are very important. This paper first introduced the support vector machine (SVM) algorithm that was used for detecting defects on the surface of paper packages. Then, the design of red wind packages was briefly described, and the simulation experiment was carried out on SVM algorithm using red wine packages with different degrees of surface defects. Proper parameters were tested using the k-fold cross-validation method. The results demonstrated that the properties of paper improved the value of packages and the SVM algorithm had better accuracy than artificial recognition in recognizing different degrees of defects on the surface of packages. In conclusion, this paper describes the application of paper in packages and provides an effective method for the defection of defects on the surface of packages. This study provides an effective references to the improvement of package values and the enhancement of package integrity.

Paper based sensor is the new technology to fabricate a simple, portable, and low cost device that exhibits the comparable properties and functions with those fabricated using complex fabrication process. Paper based sensor is usually applied in environmental monitoring, health diagnostics, and food quality control. This research is focusing on the paper based sensor that will contribute to the development of Ultraviolet (UV) sensor. The fabrication of the sensor was done by using different grade of pencil, namely 6B and 2B on different type of paper. The different grade of pencil corresponds to different percentage of graphite and clay. As for the type of paper, A4 printing paper and Whatman filter paper were used. UV sensing operation was analyzed from the measurement of current-voltage (I-V) characteristics under the exposure of UV light. Zinc oxide (ZnO) was coated on the sensor to facilitate the detection in the presence of UV. The sample fabricated using 6B pencil grade on A4 printing paper and with ZnO coating showed a better UV sensing performance compared to other samples. This is due to the high conduction of 6B pencil grade and smooth surface of A4 printing paper. The ZnO coating increased the sensor sensitivity and response towards the UV light. These findings provide valuable information which can be used in fabricating a low-cost and simple UV paper sensor.

Discovering new long non-coding RNAs (lncRNAs) has been a fundamental step in lncRNA-related research. Nowadays, many machine learning-based tools have been developed for lncRNA identification. However, many methods predict lncRNAs using sequence-derived features alone, which tend to display unstable performances on different species. Moreover, the majority of tools cannot be re-trained or tailored by users and neither can the features be customized or integrated to meet researchers’ requirements. In this study, features extracted from sequence-intrinsic composition, secondary structure and physicochemical property are comprehensively reviewed and evaluated. An integrated platform named LncFinder is also developed to enhance the performance and promote the research of lncRNA identification. LncFinder includes a novel lncRNA predictor using the heterologous features we designed. Experimental results show that our method outperforms several state-of-the-art tools on multiple species with more robust and satisfactory results. Researchers can additionally employ LncFinder to extract various classic features, build classifier with numerous machine learning algorithms and evaluate classifier performance effectively and efficiently. LncFinder can reveal the properties of lncRNA and mRNA from various perspectives and further inspire lncRNA–protein interaction prediction and lncRNA evolution analysis. It is anticipated that LncFinder can significantly facilitate lncRNA-related research, especially for the poorly explored species. LncFinder is released as R package (https://CRAN.R-project.org/package=LncFinder). A web server (http://bmbl.sdstate.edu/lncfinder/) is also developed to maximize its availability.

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. While many of these algorithms have been compared separately, a thorough and systematic evaluation of their overall performance is missing. Moreover, systematic information is lacking about the amount of missing values produced by the different proteomics software and the capabilities of different data imputation methods to account for them. In this study, we evaluated the performance of five popular quantitative label-free proteomics software workflows using four different spike-in data sets. Our extensive testing included the number of proteins quantified and the number of missing values produced by each workflow, the accuracy of detecting differential expression and logarithmic fold change and the effect of different imputation and filtering methods on the differential expression results. We found that the Progenesis software performed consistently well in the differential expression analysis and produced few missing values. The missing values produced by the other software decreased their performance, but this difference could be mitigated using proper data filtering or imputation methods. Among the imputation methods, we found that the local least squares (lls) regression imputation consistently increased the performance of the software in the differential expression analysis, and a combination of both data filtering and local least squares imputation increased performance the most in the tested data sets.

Motivation Since the dawn of the bioinformatics field, sequence alignment scores have been the main method for comparing sequences. However, alignment algorithms are quadratic, requiring long execution time. As alternatives, scientists have developed tens of alignment-free statistics for measuring the similarity between two sequences. Results We surveyed tens of alignment-free k-mer statistics. Additionally, we evaluated 33 statistics and multiplicative combinations between the statistics and/or their squares. These statistics are calculated on two k-mer histograms representing two sequences. Our evaluations using global alignment scores revealed that the majority of the statistics are sensitive and capable of finding similar sequences to a query sequence. Therefore, any of these statistics can filter out dissimilar sequences quickly. Further, we observed that multiplicative combinations of the statistics are highly correlated with the identity score. Furthermore, combinations involving sequence length difference or Earth Mover’s distance, which takes the length difference into account, are always among the highest correlated paired statistics with identity scores. Similarly, paired statistics including length difference or Earth Mover’s distance are among the best performers in finding the K-closest sequences. Interestingly, similar performance can be obtained using histograms of shorter words, resulting in reducing the memory requirement and increasing the speed remarkably. Moreover, we found that simple single statistics are sufficient for processing next-generation sequencing reads and for applications relying on local alignment. Finally, we measured the time requirement of each statistic. The survey and the evaluations will help scientists with identifying efficient alternatives to the costly alignment algorithm, saving thousands of computational hours. Availability The source code of the benchmarking tool is available as Supplementary Materials.

Mental illness is increasingly recognized as both a significant cost to society and a significant area of opportunity for biological breakthrough. As -omics and imaging technologies enable researchers to probe molecular and physiological underpinnings of multiple diseases, opportunities arise to explore the biological basis for behavioral health and disease. From individual investigators to large international consortia, researchers have generated rich data sets in the area of mental health, including genomic, transcriptomic, metabolomic, proteomic, clinical and imaging resources. General data repositories such as the Gene Expression Omnibus (GEO) and Database of Genotypes and Phenotypes (dbGaP) and mental health (MH)-specific initiatives, such as the Psychiatric Genomics Consortium, MH Research Network and PsychENCODE represent a wealth of information yet to be gleaned. At the same time, novel approaches to integrate and analyze data sets are enabling important discoveries in the area of mental and behavioral health. This review will discuss and catalog into an organizing framework the increasingly diverse set of MH data resources available, using schizophrenia as a focus area, and will describe novel and integrative approaches to molecular biomarker discovery that make use of mental health data.

Genomic data hold salient information about the characteristics of a living organism. Throughout the past decade, pinnacle developments have given us more accurate and inexpensive methods to retrieve genome sequences of humans. However, with the advancement of genomic research, there is a growing privacy concern regarding the collection, storage and analysis of such sensitive human data. Recent results show that given some background information, it is possible for an adversary to reidentify an individual from a specific genomic data set. This can reveal the current association or future susceptibility of some diseases for that individual (and sometimes the kinship between individuals) resulting in a privacy violation. Regardless of these risks, our genomic data hold much importance in analyzing the well-being of us and the future generation. Thus, in this article, we discuss the different privacy and security-related problems revolving around human genomic data. In addition, we will explore some of the cardinal cryptographic concepts, which can bring efficacy in secure and private genomic data computation. This article will relate the gaps between these two research areas-Cryptography and Genomics.

Machine learning methods and in particular random forests are promising approaches for prediction based on high dimensional omics data sets. They provide variable importance measures to rank predictors according to their predictive power. If building a prediction model is the main goal of a study, often a minimal set of variables with good prediction performance is selected. However, if the objective is the identification of involved variables to find active networks and pathways, approaches that aim to select all relevant variables should be preferred. We evaluated several variable selection procedures based on simulated data as well as publicly available experimental methylation and gene expression data. Our comparison included the Boruta algorithm, the Vita method, recurrent relative variable importance, a permutation approach and its parametric variant (Altmann) as well as recursive feature elimination (RFE). In our simulation studies, Boruta was the most powerful approach, followed closely by the Vita method. Both approaches demonstrated similar stability in variable selection, while Vita was the most robust approach under a pure null model without any predictor variables related to the outcome. In the analysis of the different experimental data sets, Vita demonstrated slightly better stability in variable selection and was less computationally intensive than Boruta. In conclusion, we recommend the Boruta and Vita approaches for the analysis of high-dimensional data sets. Vita is considerably faster than Boruta and thus more suitable for large data sets, but only Boruta can also be applied in low-dimensional settings.

The ability to collect, store and analyze massive amounts of molecular and clinical data is fundamentally transforming the scientific method and its application in translational medicine. Collecting observations has always been a prerequisite for discovery, and great leaps in scientific understanding are accompanied by an expansion of this ability. Particle physics, astronomy and climate science, for example, have all greatly benefited from the development of new technologies enabling the collection of larger and more diverse data. Unlike medicine, however, each of these fields also has a mature theoretical framework on which new data can be evaluated and incorporated—to say it another way, there are no ‘first principals’ from which a healthy human could be analytically derived. The worry, and it is a valid concern, is that, without a strong theoretical underpinning, the inundation of data will cause medical research to devolve into a haphazard enterprise without discipline or rigor. The Age of Big Data harbors tremendous opportunity for biomedical advances, but will also be treacherous and demanding on future scientists.

RNA sequencing (RNA-seq) has become a standard procedure to investigate transcriptional changes between conditions and is routinely used in research and clinics. While standard differential expression (DE) analysis between two conditions has been extensively studied, and improved over the past decades, RNA-seq time course (TC) DE analysis algorithms are still in their early stages. In this study, we compare, for the first time, existing TC RNA-seq tools on an extensive simulation data set and validated the best performing tools on published data. Surprisingly, TC tools were outperformed by the classical pairwise comparison approach on short time series (, Briefings in Bioinformatics, 20 (1), ISSN:1467-5463, ISSN:1477-4054

To detect differentially expressed genes (DEGs) in small-scale cell line experiments, usually with only two or three technical replicates for each state, the commonly used statistical methods such as significance analysis of microarrays (SAM), limma and RankProd (RP) lack statistical power, while the fold change method lacks any statistical control. In this study, we demonstrated that the within-sample relative expression orderings (REOs) of gene pairs were highly stable among technical replicates of a cell line but often widely disrupted after certain treatments such like gene knockdown, gene transfection and drug treatment. Based on this finding, we customized the RankComp algorithm, previously designed for individualized differential expression analysis through REO comparison, to identify DEGs with certain statistical control for small-scale cell line data. In both simulated and real data, the new algorithm, named CellComp, exhibited high precision with much higher sensitivity than the original RankComp, SAM, limma and RP methods. Therefore, CellComp provides an efficient tool for analyzing small-scale cell line data.

For the past 20 years, the Clusters of Orthologous Genes (COG) database had been a popular tool for microbial genome annotation and comparative genomics. Initially created for the purpose of evolutionary classification of protein families, the COG have been used, apart from straightforward functional annotation of sequenced genomes, for such tasks as (i) unification of genome annotation in groups of related organisms; (ii) identification of missing and/or undetected genes in complete microbial genomes; (iii) analysis of genomic neighborhoods, in many cases allowing prediction of novel functional systems; (iv) analysis of metabolic pathways and prediction of alternative forms of enzymes; (v) comparison of organisms by COG functional categories; and (vi) prioritization of targets for structural and functional characterization. Here we review the principles of the COG approach and discuss its key advantages and drawbacks in microbial genome analysis.

This article describes several features in the MAFFT online service for multiple sequence alignment (MSA). As a result of recent advances in sequencing technologies, huge numbers of biological sequences are available and the need for MSAs with large numbers of sequences is increasing. To extract biologically relevant information from such data, sophistication of algorithms is necessary but not sufficient. Intuitive and interactive tools for experimental biologists to semiautomatically handle large data are becoming important. We are working on development of MAFFT toward these two directions. Here, we explain (i) the Web interface for recently developed options for large data and (ii) interactive usage to refine sequence data sets and MSAs.

The overwhelming list of new bacterial genomes becoming available on a daily basis makes accurate genome annotation an essential step that ultimately determines the relevance of thousands of genomes stored in public databanks. The MicroScope platform (http://www.genoscope.cns.fr/agc/microscope) is an integrative resource that supports systematic and efficient revision of microbial genome annotation, data management and comparative analysis. Starting from the results of our syntactic, functional and relational annotation pipelines, MicroScope provides an integrated environment for the expert annotation and comparative analysis of prokaryotic genomes. It combines tools and graphical interfaces to analyze genomes and to perform the manual curation of gene function in a comparative genomics and metabolic context. In this article, we describe the free-of-charge MicroScope services for the annotation and analysis of microbial (meta)genomes, transcriptomic and re-sequencing data. Then, the functionalities of the platform are presented in a way providing practical guidance and help to the nonspecialists in bioinformatics. Newly integrated analysis tools (i.e. prediction of virulence and resistance genes in bacterial genomes) and original method recently developed (the pan-genome graph representation) are also described. Integrated environments such as MicroScope clearly contribute, through the user community, to help maintaining accurate resources.

Federation is a popular concept in building distributed cyberinfrastructures, whereby computational resources are provided by multiple organizations through a unified portal, decreasing the complexity of moving data back and forth among multiple organizations. Federation has been used in bioinformatics only to a limited extent, namely, federation of datastores, e.g. SBGrid Consortium for structural biology and Gene Expression Omnibus (GEO) for functional genomics. Here, we posit that it is important to federate both computational resources (CPU, GPU, FPGA, etc.) and datastores to support popular bioinformatics portals, with fast-increasing data volumes and increasing processing requirements. A prime example, and one that we discuss here, is in genomics and metagenomics. It is critical that the processing of the data be done without having to transport the data across large network distances. We exemplify our design and development through our experience with metagenomics-RAST (MG-RAST), the most popular metagenomics analysis pipeline. Currently, it is hosted completely at Argonne National Laboratory. However, through a recently started collaborative National Institutes of Health project, we are taking steps toward federating this infrastructure. Being a widely used resource, we have to move toward federation without disrupting 50 K annual users. In this article, we describe the computational tools that will be useful for federating a bioinformatics infrastructure and the open research challenges that we see in federating such infrastructures. It is hoped that our manuscript can serve to spur greater federation of bioinformatics infrastructures by showing the steps involved, and thus, allow them to scale to support larger user bases.

BioCyc.org is a microbial genome Web portal that combines thousands of genomes with additional information inferred by computer programs, imported from other databases and curated from the biomedical literature by biologist curators. BioCyc also provides an extensive range of query tools, visualization services and analysis software. Recent advances in BioCyc include an expansion in the content of BioCyc in terms of both the number of genomes and the types of information available for each genome; an expansion in the amount of curated content within BioCyc; and new developments in the BioCyc software tools including redesigned gene/protein pages and metabolite pages; new search tools; a new sequence-alignment tool; a new tool for visualizing groups of related metabolic pathways; and a facility called SmartTables, which enables biologists to perform analyses that previously would have required a programmer’s assistance.

Big data management for information centralization (i.e. making data of interest findable) and integration (i.e. making related data connectable) in health research is a defining challenge in biomedical informatics. While essential to create a foundation for knowledge discovery, optimized solutions to deliver high-quality and easy-to-use information resources are not thoroughly explored. In this review, we identify the gaps between current data management approaches and the need for new capacity to manage big data generated in advanced health research. Focusing on these unmet needs and well-recognized problems, we introduce state-of-the-art concepts, approaches and technologies for data management from computing academia and industry to explore improvement solutions. We explain the potential and significance of these advances for biomedical informatics. In addition, we discuss specific issues that have a great impact on technical solutions for developing the next generation of digital products (tools and data) to facilitate the raw-data-to-knowledge process in health research.

Metagenomic samples are snapshots of complex ecosystems at work. They comprise hundreds of known and unknown species, contain multiple strain variants and vary greatly within and across environments. Many microbes found in microbial communities are not easily grown in culture making their DNA sequence our only clue into their evolutionary history and biological function. Metagenomic assembly is a computational process aimed at reconstructing genes and genomes from metagenomic mixtures. Current methods have made significant strides in reconstructing DNA segments comprising operons, tandem gene arrays and syntenic blocks. Shorter, higher-throughput sequencing technologies have become the de facto standard in the field. Sequencers are now able to generate billions of short reads in only a few days. Multiple metagenomic assembly strategies, pipelines and assemblers have appeared in recent years. Owing to the inherent complexity of metagenome assembly, regardless of the assembly algorithm and sequencing method, metagenome assemblies contain errors. Recent developments in assembly validation tools have played a pivotal role in improving metagenomics assemblers. Here, we survey recent progress in the field of metagenomic assembly, provide an overview of key approaches for genomic and metagenomic assembly validation and demonstrate the insights that can be derived from assemblies through the use of assembly validation strategies. We also discuss the potential for impact of long-read technologies in metagenomics. We conclude with a discussion of future challenges and opportunities in the field of metagenomic assembly and validation.

Rank aggregation (RA), the process of combining multiple ranked lists into a single ranking, has played an important role in integrating information from individual genomic studies that address the same biological question. In previous research, attention has been focused on aggregating full lists. However, partial and/or top ranked lists are prevalent because of the great heterogeneity of genomic studies and limited resources for follow-up investigation. To be able to handle such lists, some ad hoc adjustments have been suggested in the past, but how RA methods perform on them (after the adjustments) has never been fully evaluated. In this article, a systematic framework is proposed to define different situations that may occur based on the nature of individually ranked lists. A comprehensive simulation study is conducted to examine the performance characteristics of a collection of existing RA methods that are suitable for genomic applications under various settings simulated to mimic practical situations. A non-small cell lung cancer data example is provided for further comparison. Based on our numerical results, general guidelines about which methods perform the best/worst, and under what conditions, are provided. Also, we discuss key factors that substantially affect the performance of the different methods.

The Pathosystems Resource Integration Center (PATRIC, www.patricbrc.org) is designed to provide researchers with the tools and services that they need to perform genomic and other ‘omic’ data analyses. In response to mounting concern over antimicrobial resistance (AMR), the PATRIC team has been developing new tools that help researchers understand AMR and its genetic determinants. To support comparative analyses, we have added AMR phenotype data to over 15 000 genomes in the PATRIC database, often assembling genomes from reads in public archives and collecting their associated AMR panel data from the literature to augment the collection. We have also been using this collection of AMR metadata to build machine learning-based classifiers that can predict the AMR phenotypes and the genomic regions associated with resistance for genomes being submitted to the annotation service. Likewise, we have undertaken a large AMR protein annotation effort by manually curating data from the literature and public repositories. This collection of 7370 AMR reference proteins, which contains many protein annotations (functional roles) that are unique to PATRIC and RAST, has been manually curated so that it projects stably across genomes. The collection currently projects to 1 610 744 proteins in the PATRIC database. Finally, the PATRIC Web site has been expanded to enable AMR-based custom page views so that researchers can easily explore AMR data and design experiments based on whole genomes or individual genes.

DNA methylation is one of the most extensively studied epigenetic modifications of genomic DNA. In recent years, sequencing of bisulfite-converted DNA, particularly via next-generation sequencing technologies, has become a widely popular method to study DNA methylation. This method can be readily applied to a variety of species, dramatically expanding the scope of DNA methylation studies beyond the traditionally studied human and mouse systems. In parallel to the increasing wealth of genomic methylation profiles, many statistical tools have been developed to detect differentially methylated loci (DMLs) or differentially methylated regions (DMRs) between biological conditions. We discuss and summarize several key properties of currently available tools to detect DMLs and DMRs from sequencing of bisulfite-converted DNA. However, the majority of the statistical tools developed for DML/DMR analyses have been validated using only mammalian data sets, and less priority has been placed on the analyses of invertebrate or plant DNA methylation data. We demonstrate that genomic methylation profiles of non-mammalian species are often highly distinct from those of mammalian species using examples of honey bees and humans. We then discuss how such differences in data properties may affect statistical analyses. Based on these differences, we provide three specific recommendations to improve the power and accuracy of DML and DMR analyses of invertebrate data when using currently available statistical tools. These considerations should facilitate systematic and robust analyses of DNA methylation from diverse species, thus advancing our understanding of DNA methylation.

As meta-analysis results published by consortia of genome-wide association studies (GWASs) become increasingly available, many association summary statistics-based multi-locus tests have been developed to jointly evaluate multiple single-nucleotide polymorphisms (SNPs) to reveal novel genetic architectures of various complex traits. The validity of these approaches relies on the accurate estimate of z-score correlations at considered SNPs, which in turn requires knowledge on the set of SNPs assessed by each study participating in the meta-analysis. However, this exact SNP coverage information is usually unavailable from the meta-analysis results published by GWAS consortia. In the absence of the coverage information, researchers typically estimate the z-score correlations by making oversimplified coverage assumptions. We show through real studies that such a practice can generate highly inflated type I errors, and we demonstrate the proper way to incorporate correct coverage information into multi-locus analyses. We advocate that consortia should make SNP coverage information available when posting their meta-analysis results, and that investigators who develop analytic tools for joint analyses based on summary data should pay attention to the variation in SNP coverage and adjust for it appropriately.

Switzerland has been a pioneer in the field of bioinformatics since the early 1980s. As time passed, the need for one entity to gather and represent bioinformatics on a national scale was felt and, in 1998, the SIB Swiss Institute of Bioinformatics was created. Hence, 2018 marks the Institute’s 20th anniversary. Today, the Institute federates 65 research and service groups across the country—whose activity domains range from genomics, proteomics, medicine and health to structural biology, systems biology, phylogeny and evolution—and a group whose sole task is dedicated to training. The Institute hosts 12 competence centres that provide bioinformatics and biocuration expertise to life scientists across the country. SIB sensed early on that the wealth of data produced by modern technologies in medicine and the growing self-awareness of patients was about to revolutionize the way medical data are considered. In 2012, it created a Clinical Bioinformatics group to address the issue of personalized health, thus working towards a more global approach to patient management, and more targeted and effective therapies. In this respect, SIB has a major role in the Swiss Personalized Health Network to make patient-related data available to research throughout the country. The uniqueness of the Institute’s governance structure has also inspired the structure of other European life science organizations, notably ELIXIR.

EMBL Australia Bioinformatics Resource (EMBL-ABR) is a developing national research infrastructure, providing bioinformatics resources and support to life science and biomedical researchers in Australia. EMBL-ABR comprises 10 geographically distributed national nodes with one coordinating hub, with current funding provided through Bioplatforms Australia and the University of Melbourne for its initial 2-year development phase. The EMBL-ABR mission is to: (1) increase Australia’s capacity in bioinformatics and data sciences; (2) contribute to the development of training in bioinformatics skills; (3) showcase Australian data sets at an international level and (4) enable engagement in international programs. The activities of EMBL-ABR are focussed in six key areas, aligning with comparable international initiatives such as ELIXIR, CyVerse and NIH Commons. These key areas—Tools, Data, Standards, Platforms, Compute and Training—are described in this article.

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. Thus, next-generation phylogenomics must address computational scalability while rethinking the nature of orthogroups, the alignment of multiple sequences and the inference and comparison of trees. New phylogenomic workflows have begun to take shape based on so-called alignment-free (AF) approaches. Here, we review the conceptual foundations of AF phylogenetics for the hierarchical (vertical) and reticulate (lateral) components of genome evolution, focusing on methods based on k-mers. We reflect on what seems to be successful, and on where further development is needed.

Diverse forms of resistance to anticancer drugs can lead to the failure of chemotherapy. Drug resistance is one of the most intractable issues for successfully treating cancer in current clinical practice. Effective clinical approaches that could counter drug resistance by restoring the sensitivity of tumors to the targeted agents are urgently needed. As numerous experimental results on resistance mechanisms have been obtained and a mass of high-throughput data has been accumulated, mathematical modeling and computational predictions using systematic and quantitative approaches have become increasingly important, as they can potentially provide deeper insights into resistance mechanisms, generate novel hypotheses or suggest promising treatment strategies for future testing. In this review, we first briefly summarize the current progress of experimentally revealed resistance mechanisms of targeted therapy, including genetic mechanisms, epigenetic mechanisms, posttranslational mechanisms, cellular mechanisms, microenvironmental mechanisms and pharmacokinetic mechanisms. Subsequently, we list several currently available databases and Web-based tools related to drug sensitivity and resistance. Then, we focus primarily on introducing some state-of-the-art computational methods used in drug resistance studies, including mechanism-based mathematical modeling approaches (e.g. molecular dynamics simulation, kinetic model of molecular networks, ordinary differential equation model of cellular dynamics, stochastic model, partial differential equation model, agent-based model, pharmacokinetic–pharmacodynamic model, etc.) and data-driven prediction methods (e.g. omics data-based conventional screening approach for node biomarkers, static network approach for edge biomarkers and module biomarkers, dynamic network approach for dynamic network biomarkers and dynamic module network biomarkers, etc.). Finally, we discuss several further questions and future directions for the use of computational methods for studying drug resistance, including inferring drug-induced signaling networks, multiscale modeling, drug combinations and precision medicine.

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. It is important to design a study that produces statistically accurate and reliable results. Power computation methods have been well established for both microarray-based gene expression studies and genotyping microarray-based genome-wide association studies. High-throughput sequencing (HTS) has greatly enhanced our ability to conduct biomedical studies at the highest possible resolution (per nucleotide). However, the complexity of power computations is much greater for sequencing data than for the simpler genotyping array data. Research on methods of power computations for HTS-based studies has been recently conducted but is not yet well known or widely used. In this article, we describe the power computation methods that are currently available for a range of HTS-based studies, including DNA sequencing, RNA-sequencing, microbiome sequencing and chromatin immunoprecipitation sequencing. Most importantly, we review the methods of power analysis for several types of sequencing data and guide the reader to the relevant methods for each data type.

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. There are lots of challenges on both steps in a scenario of complicated data and lacking of sufficient domain knowledge. The latest advances in deep learning technologies provide new effective paradigms to obtain end-to-end learning models from complex data. In this article, we review the recent literature on applying deep learning technologies to advance the health care domain. Based on the analyzed work, we suggest that deep learning approaches could be the vehicle for translating big biomedical data into improved human health. However, we also note limitations and needs for improved methods development and applications, especially in terms of ease-of-understanding for domain experts and citizen scientists. We discuss such challenges and suggest developing holistic and meaningful interpretable architectures to bridge deep learning models and human interpretability.

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. Surprisingly, our results show that the bipartite topology alone, if adequately exploited by means of the recently proposed local-community-paradigm (LCP) theory—initially detected in brain-network topological self-organization and afterwards generalized to any complex network—is able to suggest highly reliable predictions, with comparable performance with the state-of-the-art-supervised methods that exploit additional (non-topological, for instance biochemical) DTI knowledge. Furthermore, a detailed analysis of the novel predictions revealed that each class of methods prioritizes distinct true interactions; hence, combining methodologies based on diverse principles represents a promising strategy to improve drug–target discovery. To conclude, this study promotes the power of bio-inspired computing, demonstrating that simple unsupervised rules inspired by principles of topological self-organization and adaptiveness arising during learning in living intelligent systems (like the brain) can efficiently equal perform complicated algorithms based on advanced, supervised and knowledge-based engineering.

The German Network for Bioinformatics Infrastructure (de.NBI) is a national initiative funded by the German Federal Ministry of Education and Research (BMBF). The mission of de.NBI is (i) to provide high-quality bioinformatics services to users in basic and applied life sciences research from academia, industry and biomedicine; (ii) to offer bioinformatics training to users in Germany and Europe through a wide range of workshops and courses; and (iii) to foster the cooperation of the German bioinformatics community with international network structures such as the European life-sciences Infrastructure for biological Information (ELIXIR). The network was launched by the BMBF in March 2015 and now includes 40 service projects operated by 30 project partners that are organized in eight service centers. The de.NBI staff develops further and maintains almost 100 bioinformatics services for the human, plant and microbial research fields and provides comprehensive training courses to support users with different expertise levels in bioinformatics. In the future, de.NBI will expand its activities to the European level, as the de.NBI consortium was assigned by the BMBF to establish and run the German node of ELIXIR. The Author 2017. Published by Oxford University Press.

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. At the heart of computational phenotype analysis are the phenotype ontologies. A large number of these ontologies have been developed across many domains, and we are now at a point where the knowledge captured in the structure of these ontologies can be used for the integration and analysis of large interrelated data sets. The Phenotype And Trait Ontology framework provides a method for formal definitions of phenotypes and associated data sets and has proved to be key to our ability to develop methods for the integration and analysis of phenotype data. Here, we describe the development and products of the ontological approach to phenotype capture, the formal content of phenotype ontologies and how their content can be used computationally.

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. Several computational methods have been developed to identify differential methylation using bisulfite sequencing data; however, there is no clear consensus among existing approaches. A comprehensive survey of these approaches would be of great benefit to potential users and researchers to get a complete picture of the available resources. In this article, we present a detailed survey of 22 such approaches focusing on their underlying statistical models, primary features, key advantages and major limitations. Importantly, the intrinsic drawbacks of the approaches pointed out in this survey could potentially be addressed by future research.

Small RNAs (sRNAs) are important short-length molecules with regulatory functions essential for plant development and plasticity. High-throughput sequencing of total sRNA populations has revealed that the largest share of sRNA remains uncategorized. To better understand the role of sRNA-mediated cellular regulation, it is necessary to create accurate and comprehensive catalogues of sRNA and their sequence features, a task that currently relies on nontrivial bioinformatic approaches. Although a large number of computational tools have been developed to predict features of sRNA sequences, these tools are mostly dedicated to microRNAs and none integrates the functionalities necessary to describe units from all sRNA pathways thus far discovered in plants. Here, we review the different classes of sRNA found in plants and describe available bioinformatics tools that can help in their detection and categorization.

This review provides a historical overview of the inception and development of bioinformatics research in the Netherlands. Rooted in theoretical biology by foundational figures such as Paulien Hogeweg (at Utrecht University since the 1970s), the developments leading to organizational structures supporting a relatively large Dutch bioinformatics community will be reviewed. We will show that the most valuable resource that we have built over these years is the close-knit national expert community that is well engaged in basic and translational life science research programmes. The Dutch bioinformatics community is accustomed to facing the ever-changing landscape of data challenges and working towards solutions together. In addition, this community is the stable factor on the road towards sustainability, especially in times where existing funding models are challenged and change rapidly.

Investing in documenting your bioinformatics software well can increase its impact and save your time. To maximize the effectiveness of your documentation, we suggest following a few guidelines we propose here. We recommend providing multiple avenues for users to use your research software, including a navigable HTML interface with a quick start, useful help messages with detailed explanation and thorough examples for each feature of your software. By following these guidelines, you can assure that your hard work maximally benefits yourself and others.

Resumo Estudos têm contribuído para a definição de importantes diretrizes acerca da conservação de documentos de arquivo e, em especial, a conservação preventiva, fomentando a discussão e a consolidação de políticas que busquem auxiliar na preservação dos acervos. Nessa perspectiva, a presente pesquisa, realizada em parceria entre o Instituto de Ciências Humanas e da Informação - curso de Arquivologia -, e a Escola de Química e Alimentos da Universidade Federal do Rio Grande, tem como objetivo avaliar possíveis ações de danos provocados pelo uso das folhas autoadesivas nos documentos textuais em suporte papel, visando contribuir com as discussões e estudos sobre a temática de conservação e preservação dos acervos. A metodologia para o desenvolvimento deste trabalho foi dividida em etapas que consistiram em: seleção da amostragem e pesquisa sobre o surgimento dos blocos autoadesivos, revisão do referencial teórico, análise dos dados coletados través da técnica de microscopia eletrônica de varredura e posterior divulgação dos resultados da pesquisa. Abstract Studies have contributed to the definition of important guidelines on the file record keeping and in particular preventive conservation fostering discussion and the consolidation of policies that seek to assist in the preservation of collections. In this perspective the present research, which is a work in partnership between the Institute of Humanities and information - Archivology course, and the School of Chemistry and Food, Universidade Federal do Rio Grande, aims to evaluate possible actions deterioration caused by the use of self-adhesive sheets in textual paper documents, to contribute to discussions and studies on the theme of conservation and preservation of collections. The methodology for the development of this work has been divided into steps that were: the sample selection and research on the emergence of adhesive plates, review the theoretical framework, analysis of data collected slant electron microscopy technique and subsequent dissemination of research results.

To minimize exposure dose during lateral spine X-Ray testing and obtain optimal image for diagnosis a water filter was made to measure and evaluate dose distribution. When applying the water filter, as thickness increased exposure dose decreased. When applying 2 cm of water filter, clarity of contrast and boundary was found to be 4.5 ± 0.5 and resolution was found to be 2.00 ± 0.5 Lp/mm which was almost identical image quality compared to not applying water filter which showed clarity of contrast and boundary of 5.0 ± 0.0, and resolution of 2.50 ± 0.0 Lp/mm, while reducing exposure dose by 55%. This result is expected to have many uses as important basic data to predict exposure dose of patients and to minimize medical exposure dose through applying water filters during lateral spine X-Ray testing.

In the era of big data and artificial intelligence, public datasets are becoming increasingly important for researchers to build and evaluate their models. This paper presents the FIKWaste dataset, which contains time series data for the volume of waste produced in three restaurant kitchens in Portugal. Organic (undifferentiated) and inorganic (glass, paper, and plastic) waste bins were monitored for a consecutive period of four weeks. In addition to the time series measurements, the FIKWaste dataset contains labels for waste disposal events, i.e., when the waste bins are emptied, and technical and non-technical details of the monitored kitchens.

Sustainable noncommercial bioinformatics infrastructures are a prerequisite to use and take advantage of the potential of big data analysis for research and economy. Consequently, funders, universities and institutes as well as users ask for a transparent value model for the tools and services offered. In this article, a generally applicable lightweight method is described by which bioinformatics infrastructure projects can estimate the value of tools and services offered without determining exactly the total costs of ownership. Five representative scenarios for value estimation from a rough estimation to a detailed breakdown of costs are presented. To account for the diversity in bioinformatics applications and services, the notion of service-specific ‘service provision units’ is introduced together with the factors influencing them and the main underlying assumptions for these ‘value influencing factors’. Special attention is given on how to handle personnel costs and indirect costs such as electricity. Four examples are presented for the calculation of the value of tools and services provided by the German Network for Bioinformatics Infrastructure (de.NBI): one for tool usage, one for (Web-based) database analyses, one for consulting services and one for bioinformatics training events. Finally, from the discussed values, the costs of direct funding and the costs of payment of services by funded projects are calculated and compared.

Many drugs are derived from small molecules produced by microorganisms and plants, so-called natural products. Natural products have diverse chemical structures, but the biosynthetic pathways producing those compounds are often organized as biosynthetic gene clusters (BGCs) and follow a highly conserved biosynthetic logic. This allows for the identification of core biosynthetic enzymes using genome mining strategies that are based on the sequence similarity of the involved enzymes/genes. However, mining for a variety of BGCs quickly approaches a complexity level where manual analyses are no longer possible and require the use of automated genome mining pipelines, such as the antiSMASH software. In this review, we discuss the principles underlying the predictions of antiSMASH and other tools and provide practical advice for their application. Furthermore, we discuss important caveats such as rule-based BGC detection, sequence and annotation quality and cluster boundary prediction, which all have to be considered while planning for, performing and analyzing the results of genome mining studies.

International audience; The size of available graphs has drastically increased in recent years. The real-time visualization of graphs with millions of edges is a challenge but is necessary to grasp information hidden in huge datasets. This article presents an end-to-end technique to visualize huge graphs using an established Big Data ecosystem and a lightweight client running in a Web browser. For that purpose, levels of abstraction and graph tiles are generated by a batch layer and the interactive visualization is provided using a serving layer and client-side real-time computation of edge bundling and graph splatting. A major challenge is to create techniques that work without moving data to an ad hoc system and that take advantage of the horizontal scalability of these infrastructures. We introduce two novel scalable algorithms that enable to generate a canopy clustering and to aggregate graph edges. These two algorithms are both used to produce levels of abstraction and graph tiles. We prove that our technique guarantee a quality of visualization by controlling both the necessary bandwidth required for data transfer and the quality of the produced visualization. Furthermore, we demonstrate the usability of our technique by providing a complete prototype. We present benchmarks on graphs with millions of elements and we compare our results to those obtained by state of the art techniques. Our results show that new Big Data technologies can be incorporated into visualization pipeline to push out the size limits of graphs one can visually analyze.

Transcription factor and microRNA (miRNA) can mutually regulate each other and jointly regulate their shared target genes to form feed-forward loops (FFLs). While there are many studies of dysregulated FFLs in a specific cancer, a systematic investigation of dysregulated FFLs across multiple tumor types (pan-cancer FFLs) has not been performed yet. In this study, using The Cancer Genome Atlas data, we identified 26 pan-cancer FFLs, which were dysregulated in at least five tumor types. These pan-cancer FFLs could communicate with each other and form functionally consistent subnetworks, such as epithelial to mesenchymal transition-related subnetwork. Many proteins and miRNAs in each subnetwork belong to the same protein and miRNA family, respectively. Importantly, cancer-associated genes and drug targets were enriched in these pan-cancer FFLs, in which the genes and miRNAs also tended to be hubs and bottlenecks. Finally, we identified potential anticancer indications for existing drugs with novel mechanism of action. Collectively, this study highlights the potential of pan-cancer FFLs as a novel paradigm in elucidating pathogenesis of cancer and developing anticancer drugs.

While novel technologies such as high-throughput screening have advanced together with significant investment by pharmaceutical companies during the past decades, the success rate for drug development has not yet been improved prompting researchers looking for new strategies of drug discovery. Drug repositioning is a potential approach to solve this dilemma. However, experimental identification and validation of potential drug targets encoded by the human genome is both costly and time-consuming. Therefore, effective computational approaches have been proposed to facilitate drug repositioning, which have proved to be successful in drug discovery. Doubtlessly, the availability of open-accessible data from basic chemical biology research and the success of human genome sequencing are crucial to develop effective in silico drug repositioning methods allowing the identification of potential targets for existing drugs. In this work, we review several chemogenomic data-driven computational algorithms with source codes publicly accessible for predicting drug–target interactions (DTIs). We organize these algorithms by model properties and model evolutionary relationships. We re-implemented five representative algorithms in R programming language, and compared these algorithms by means of mean percentile ranking, a new recall-based evaluation metric in the DTI prediction research field. We anticipate that this review will be objective and helpful to researchers who would like to further improve existing algorithms or need to choose appropriate algorithms to infer potential DTIs in the projects. The source codes for DTI predictions are available at: https://github.com/minghao2016/chemogenomicAlg4DTIpred.

Precision medicine is rapidly emerging as a strategy to tailor medical treatment to a small group or even individual patients based on their genetics, environment and lifestyle. Precision medicine relies heavily on developments in systems biology and omics disciplines, including metabolomics. Combination of metabolomics with sophisticated bioinformatics analysis and mathematical modeling has an extreme power to provide a metabolic snapshot of the patient over the course of disease and treatment or classifying patients into subpopulations and subgroups requiring individual medical treatment. Although a powerful approach, metabolomics have certain limitations in technology and bioinformatics. We will review various aspects of metabolomics technology and bioinformatics, from data generation, bioinformatics analysis, data fusion and mathematical modeling to data management, in the context of precision medicine.