Bioinformatics tools and databases for analysis of next-generation sequence data

Genome sequencing has been revolutionized by next-generation technologies, which can rapidly produce vast quantities of data at relatively low cost. With data production now no longer being limited, there is a huge challenge to analyse the data flood and interpret biological meaning. Bioinformatics scientists have risen to the challenge and a large number of software tools and databases have been produced and these continue to evolve with this rapidly advancing field. Here, we outline some of the tools and databases commonly used for the analysis of next-generation sequence data with comment on their utility.     

Computational databases, pathway and cheminformatics tools for tuberculosis drug discovery

We are witnessing the growing menace of both increasing cases of drug-sensitive and drug-resistant Mycobacterium tuberculosis strains and the challenge to produce the first new tuberculosis (TB) drug in well over 40 years. The TB community, having invested in extensive high-throughput screening efforts, is faced with the question of how to optimally leverage these data to move from a hit to a lead to a clinical candidate and potentially, a new drug. Complementing this approach, yet conducted on a much smaller scale, cheminformatic techniques have been leveraged and are examined in this review. We suggest that these computational approaches should be optimally integrated within a workflow with experimental approaches to accelerate TB drug discovery.     

Bioinformatics databases and tools in virology research: an overview

Viruses are major factors of human infectious diseases. Understanding of the structure-function correlation in viruses is important for the identification of potential anti-viral inhibitors and vaccine targets. In virology research, virus-related databases and bioinformatic analysis tools are essential for discerning relationships within complex datasets about viruses and host-virus interactions. Bioinformatic analyses on viruses include the identification of open reading frames, gene prediction, homology searching, sequence alignment, and motif and epitope recognition. The predictions of features such as transmembrane domains, glycosylation sites, and protein secondary and tertiary structure are important for analyzing the structure-function relationship of proteins encoded in viral genomes. Biochemical pathway analysis can help elucidate information at the biological systems level. Microarray analysis provides methods for high throughput screening and gene expression profiling. Virus-related bioinformatics databases include those concerned with viral sequences, taxonomy, homologous protein families, structures, or dedicated to specific viruses such as influenza and herpes simplex virus (HSV). This review provides a guide and overview of computational programs for these analyses as a resource for genomics and proteomics studies in virology research. These resources are useful for understanding viral diseases, as well as for the design and development of anti-viral agents.     

再论可持续性科学: 新形势与新机遇

近10年来,可持续性科学蓬勃发展,已成为21世纪全球普遍关注的一个重要的新科学领域.然而,在大力提倡可持续发展和生态文明建设的中国,可持续性科学尚未引起科学家和实践者的足够重视.为促进可持续性科学在中国的发展,2014年邬建国等曾撰文介绍什么是可持续性科学.本文进一步探讨了这一问题,并补充阐述了可持续性科学与可持续发展研究的关系、可持续性科学的科学范式及其8个基本论题.基于对可持续性科学发展动态的分析,作者认为,一方面,可持续性科学已进入系统推进的成熟发展期;另一方面,虽然我国可持续发展研究、实践与教育的热情高涨,但在可持续性科学领域起步较晚,落后于主要发达国家和南非.为此,本文在文献综述的基础上,提出促进中国发展可持续性科学的“三位一体”策略:一是“请进来”以服务中国实践;二是“走出去”以贡献中国智慧;三是“中西医结合”以引领学科发展.     

Cloud-hosted databases: technologies,challenges and opportunities

One of the main advantages of the cloud computing paradigm is that it simplifies the time-consuming processes of hardware provisioning, hardware purchasing and software deployment. Currently, we are witnessing a proliferation in the number of cloud-hosted applications with a tremendous increase in the scale of the data generated as well as being consumed by such applications. Cloud-hosted database systems powering these applications form a critical component in the software stack of these applications. To better understand the challenges in developing effective cloud-hosted database systems, this article discusses the existing technologies for hosting the database tier of software applications in cloud environments, illustrates their strengths and weaknesses, and presents some opportunities for future work.     

HDL revisited: new opportunities for managing dyslipoproteinaemia and cardiovascular disease

Low concentrations of high-density lipoprotein (HDL) cholesterol constitute a risk factor for coronary heart disease (CHD). There is increasing evidence that increasing HDL-cholesterol levels reduces cardiovascular risk. The phenotype of low HDL cholesterol with or without elevated triglycerides is common and it is characteristic of patients with central obesity, insulin resistance, hypertension and type 2 diabetes mellitus; conditions associated with increased cardiovascular risk and are part of the rubric of the metabolic syndrome. Epidemiological, experimental and clinical trial evidence suggests that there is a good rationale for raising HDL-cholesterol in these and other high-risk patients. The protective effect of HDL-cholesterol against atherosclerosis and cardiovascular disease is mediated by both enhanced reverse cholesterol transport (RCT) and by direct anti-atherosclerotic mechanisms. Recent studies have elucidated mechanisms whereby HDL acts to reduce cardiovascular risk, supporting the rationale for targeting of HDL with lipid-modifying therapy. Ongoing investigation of mechanisms by which HDL acts to reduce the risk of atherosclerosis will provide opportunities for the development of new therapeutic strategies to decrease the risk of atherosclerosis.     

The Personal Sequence Database: a suite of tools to create and maintain web-accessible sequence databases

Background  

Large molecular sequence databases are fundamental resources for modern bioscientists. Whether for project-specific purposes or sharing data with colleagues, it is often advantageous to maintain smaller sequence databases. However, this is usually not an easy task for the average bench scientist.     

p53 and APC gene mutations: software and databases.

A large number of different mutations in the APC and p53 tumor suppressor genes have been identified in various types of cancer. This substantial increase since our previous reports can enable analyses which were not previously possible. In order to capture all these new data, the software permitting analysis has been improved. This report describes the various improvements since the second release of the database.     

PEPPLOT, a protein secondary structure analysis program for the UWGCG sequence analysis software package.

We describe a program for the analysis of protein secondary structure that operates with the Sequence Analysis Software Package of the University of Wisconsin Genetics Computer Group (UWGCG). The program produces both graphic and printed output. Structure prediction using the Chou and Fasman and Robson et al methods, and hydropathy analysis by the method of Kyte and Doolittle are included along with a simplified method of hydrophobic moment analysis. The power of the program is the coordinated presentation of many different kinds of structural information on the same plot.     

Harnessing Nutrigenomics: Development of web-based communication, databases, resources, and tools

Nutrient - gene interactions are responsible for maintaining health and preventing or delaying disease. Unbalanced diets for a given genotype lead to chronic diseases such as obesity, diabetes, cardiovascular, and are likely to contribute to increased severity and/or early-onset of many age-related diseases. Many nutrition and many genetic studies still fail to properly include both variables in the design, execution, and analyses of human, laboratory animal, or cell culture experiments. The complexity ofnutrient-gene interactions has led to the realization that strategic international alliances are needed to improve the completeness of nutrigenomic studies - a task beyond the capabilities of a single laboratory team. Eighty-eight researchers from 22 countries recently outlined the issues and challenges for harnessing the nutritional genomics for public and personal health. The next step in the process of forming productive international alliances is the development of a virtual center for organizing collaborations and communications that foster resources sharing, best practices improvements, and creation of databases. We describe here plans and initial efforts of creating the Nutrigenomics Information Portal, a web-based resource for the international nutrigenomics society. This portal aims at becoming the prime source ofinformation and interaction for nutrigenomics scientists through a collaborative effort.     

DNA sequence analysis linguistic tools: contrast vocabularies, compositional spectra and linguistic complexity

This is a review of the methods based on counting oligomers in nucleotide and amino acid sequences. Such methods are analogous to the formal linguistic analysis of human texts. This review includes methods based on the calculation of observed occurrences (frequencies) of oligomers and their distribution, as well as those based on deviations between the observed and the expected occurrences (contrast words, genome signatures) in biological sequences. Both types of methods have a wide range of sensitivity and can identify homologous as well as functionally and taxonomically related sequences.     

Polyploidy and its effect on evolutionary success: old questions revisited with new tools

Polyploidy, the condition of possessing more than two complete genomes in a cell, has intrigued biologists for almost a century. Polyploidy is found in many plants and some animal species and today we know that polyploidy has had a role in the evolution of all angiosperms. Despite its widespread occurrence, the direct effect of polyploidy on evolutionary success of a species is still largely unknown. Over the years many attractive hypotheses have been proposed in an attempt to assign functionality to the increased content of a duplicated genome. Among these hypotheses are the proposal that genome doubling confers distinct advantages to a polyploid and that these advantages allow polyploids to thrive in environments that pose challenges to the polyploid''s diploid progenitors. This article revisits these long-standing questions and explores how the integration of recent genomic developments with ecological, physiological and evolutionary perspectives has contributed to addressing unresolved problems about the role of polyploidy. Although unsatisfactory, the current conclusion has to be that despite significant progress, there still isn''t enough information to unequivocally answer many unresolved questions about cause and effect of polyploidy on evolutionary success of a species. There is, however, reason to believe that the increasingly integrative approaches discussed here should allow us in the future to make more direct connections between the effects of polyploidy on the genome and the responses this condition elicits from the organism living in its natural environment.     

Suspension array technology: new tools for gene and protein analysis.

Flow cytometry has long been a key tool in the analysis of lymphocytes and other cells, owing to its ability to make quantitative, homogeneous, multiparameter measurements of particles. New developments in illumination sources, digital signal processing and microsphere chemistry are driving the development of flow cytometry in new areas of biomedical research. In particular. the maturation of approaches to perform highly parallel analyses using suspension arrays of microspheres with different morphospectral features is making flow cytometry an important tool in protein and genetic analysis. In this paper, we review the development of suspension array technology (SAT), current applications in protein and genomic analysis, and the prospects for this platform in a variety of large scale screening applications.     

Pathway databases and tools for their exploitation: benefits,current limitations and challenges

In past years, comprehensive representations of cell signalling pathways have been developed by manual curation from literature, which requires huge effort and would benefit from information stored in databases and from automatic retrieval and integration methods. Once a reconstruction of the network of interactions is achieved, analysis of its structural features and its dynamic behaviour can take place. Mathematical modelling techniques are used to simulate the complex behaviour of cell signalling networks, which ultimately sheds light on the mechanisms leading to complex diseases or helps in the identification of drug targets. A variety of databases containing information on cell signalling pathways have been developed in conjunction with methodologies to access and analyse the data. In principle, the scenario is prepared to make the most of this information for the analysis of the dynamics of signalling pathways. However, are the knowledge repositories of signalling pathways ready to realize the systems biology promise? In this article we aim to initiate this discussion and to provide some insights on this issue.     

Analysis of conserved domains and sequence motifs in cellular regulatory proteins and locus control regions using new software tools for multiple alignment and visualization.

With the tremendous expansion of molecular sequence data in recent years, multiple alignment is arguably one of the two most important analytic techniques (the other being fast database searching). A number of useful approaches to this problem have previously been developed, but often they are limited to only a subset of multiple-alignment applications and cannot easily deal with the complex structural organization seen in an increasing number of sequences. For example, a single sequence may contain several domains of different evolutionary origins, and the multiplicities and relative ordering of these domains may be quite different among related sequences. Here we describe an integrated set of interactive Unix tools that combines several multiple-alignment techniques with traditional "dot-plot" visualization to provide a flexible environment for approaching complex sequence analysis problems. We apply these tools to the identification and characterization of "catalytic" domains in ras and rho/rac GTPase-activating proteins, to "Src homology" (SH2, SH3) domains in cytoplasmic signaling proteins, to repetitive sequence motifs in the alpha and beta subunits of protein prenyltransferases, and to regulatory DNA sequences in the locus control region of the beta-globin gene cluster.