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MetaBasis: a web-based database containing metadata on software tools and databases in the field of bioinformatics.

UNLABELLED: We have developed an integrated web-based relational database information system, which offers an extensive search functionality of validated entries containing available bioinformatics computing resources. This system, called MetaBasis, aims to provide the bioinformatics community, and especially newcomers to the field, with easy access to reliable bioinformatics databases and tools. MetaBasis is focused on non-commercial and open-source software tools. AVAILABILITY: http://metabasis.bioacademy.gr/

Computational Biology↗

Atlas - a data warehouse for integrative bioinformatics.

BACKGROUND: We present a biological data warehouse called Atlas that locally stores and integrates biological sequences, molecular interactions, homology information, functional annotations of genes, and biological ontologies. The goal of the system is to provide data, as well as a software infrastructure for bioinformatics research and development. DESCRIPTION: The Atlas system is based on relational data models that we developed for each of the source data types. Data stored within these relational models are managed through Structured Query Language (SQL) calls that are implemented in a set of Application Programming Interfaces (APIs). The APIs include three languages: C++, Java, and Perl. The methods in these API libraries are used to construct a set of loader applications, which parse and load the source datasets into the Atlas database, and a set of toolbox applications which facilitate data retrieval. Atlas stores and integrates local instances of GenBank, RefSeq, UniProt, Human Protein Reference Database (HPRD), Biomolecular Interaction Network Database (BIND), Database of Interacting Proteins (DIP), Molecular Interactions Database (MINT), IntAct, NCBI Taxonomy, Gene Ontology (GO), Online Mendelian Inheritance in Man (OMIM), LocusLink, Entrez Gene and HomoloGene. The retrieval APIs and toolbox applications are critical components that offer end-users flexible, easy, integrated access to this data. We present use cases that use Atlas to integrate these sources for genome annotation, inference of molecular interactions across species, and gene-disease associations. CONCLUSION: The Atlas biological data warehouse serves as data infrastructure for bioinformatics research and development. It forms the backbone of the research activities in our laboratory and facilitates the integration of disparate, heterogeneous biological sources of data enabling new scientific inferences. Atlas achieves integration of diverse data sets at two levels. First, Atlas stores data of similar types using common data models, enforcing the relationships between data types. Second, integration is achieved through a combination of APIs, ontology, and tools. The Atlas software is freely available under the GNU General Public License at: http://bioinformatics.ubc.ca/atlas/

Computational Biology↗

Clinical bioinformatics.

Clinical bioinformatics provides biological and medical information to allow for individualized healthcare. In this review, we describe the uses of clinical bioinformatics. After the analysis of the complete human genome sequences, clinical bioinformatics enables researchers to search online biological databases and use the biological information in their medical practices. The data obtained from using microarray is extremely complicated. In clinical bioinformatics, selecting appropriate software to analyze the microarray data for medical decision making is crucial. Proteomics strategy tools usually focus on similarity searches, structure prediction, and protein modeling. In clinical bioinformatics, the proteomic data only have meaning if they are integrated with clinical data. In pharmacogenomics, clinical bioinformatics includes elaborate studies of bioinformatics tools and various facets of proteomics related to drug target identification and clinical validation. Using clinical bioinformatics, researchers apply computational and high-throughput experimental techniques to cancer research and systems biology. Meanwhile, researchers of bioinformatics and medical information have incorporated clinical bioinformatics to improve health care, using biological and medical information. Using the high volume of biological information from clinical bioinformatics will contribute to changes in practice standards in the healthcare system. We believe that clinical bioinformatics provides benefits of improving healthcare, disease prevention and health maintenance as we move toward the era of personalized medicine.

Computational Biology↗

Data standards for flow cytometry.

Flow cytometry (FCM) is an analytical tool widely used for cancer and HIV/AIDS research, and treatment, stem cell manipulation and detecting microorganisms in environmental samples. Current data standards do not capture the full scope of FCM experiments and there is a demand for software tools that can assist in the exploration and analysis of large FCM datasets. We are implementing a standardized approach to capturing, analyzing, and disseminating FCM data that will facilitate both more complex analyses and analysis of datasets that could not previously be efficiently studied. Initial work has focused on developing a community-based guideline for recording and reporting the details of FCM experiments. Open source software tools that implement this standard are being created, with an emphasis on facilitating reproducible and extensible data analyses. As well, tools for electronic collaboration will assist the integrated access and comprehension of experiments to empower users to collaborate on FCM analyses. This coordinated, joint development of bioinformatics standards and software tools for FCM data analysis has the potential to greatly facilitate both basic and clinical research--impacting a notably diverse range of medical and environmental research areas.

Cell Separation↗

A comprehensive software suite for the analysis of cDNAs.

We have developed a comprehensive software suite for bioinformatics research of cDNAs; it is aimed at rapid characterization of the features of genes and the proteins they code. Methods implemented include the detection of translation initiation and termination signals, statistical analysis of codon usage, comparative study of amino acid composition, comparative modeling of the structures of product proteins, prediction of alternative splice forms, and metabolic pathway reconstruction.

Alternative Splicing↗

DNA microarray analysis of striatal gene expression in symptomatic transgenic Huntington's mice (R6/2) reveals neuroinflammation and insulin associations.

Huntington's disease (HD) is an inherited, progressive neurodegenerative disorder caused by CAG repeat expansion in the gene that codes for the protein huntingtin. The underlying neuropathological events leading to the selectivity of striatal neuronal loss are unknown. However, the huntingtin mutation interferes at several levels of normal cell function. The complexity of this disease makes microarray analysis an appealing technique to begin the identification of common pathways that may contribute to the pathology. In this study, striatal tissue was extracted for gene expression profiling from wild-type and symptomatic transgenic Huntington mice (R6/2) expressing part of the human Huntington's disease gene. We interrogated a 15 K high-density mouse EST array not previously used for HD and identified 170 significantly differentially expressed ESTs in symptomatic R6/2 mice. Of the 80 genes with known function, 9 genes had previously been identified as altered in HD. 71 known genes were associated with HD for the first time. The data obtained from this study confirm and extend previous observations using DNA microarray techniques on genetic models for HD, revealing novel changes in expression in a number of genes not previously associated with HD. Further bioinformatic analysis, using software to construct biological association maps, focused attention on proteins such as insulin and TH1-mediated cytokines, suggesting that they may be important regulators of affected genes. These results may provide insight into the regulation and interaction of genes that contribute to adaptive and pathological processes involved in HD.

Animals↗

Identification of novel candidate oncogenes and tumor suppressors in malignant pleural mesothelioma using large-scale transcriptional profiling.

Malignant pleural mesothelioma (MPM) is a highly lethal, poorly understood neoplasm that is typically associated with asbestos exposure. We performed transcriptional profiling using high-density oligonucleotide microarrays containing approximately 22,000 genes to elucidate potential molecular and pathobiological pathways in MPM using discarded human MPM tumor specimens (n = 40), normal lung specimens (n = 4), normal pleura specimens (n = 5), and MPM and SV40-immortalized mesothelial cell lines (n = 5). In global expression analysis using unsupervised clustering techniques, we found two potential subclasses of mesothelioma that correlated loosely with tumor histology. We also identified sets of genes with expression levels that distinguish between multiple tumor subclasses, normal and tumor tissues, and tumors with different morphologies. Microarray gene expression data were confirmed using quantitative reverse transcriptase-polymerase chain reaction and protein analysis for three novel candidate oncogenes (NME2, CRI1, and PDGFC) and one candidate tumor suppressor (GSN). Finally, we used bioinformatics tools (ie, software) to create and explore complex physiological pathways. Combined, all of these data may advance our understanding of mesothelioma tumorigenesis, pathobiology, or both.

Blotting, Western↗

BIWT: a bioinformatics walkthrough for embedding spatial multiomics in agent-based models for virtual cells.

SUMMARY: Whereas transcriptomic and spatial profiling offer static snapshots of tissue structure, mechanistic models use biological rules to predict how tissues evolve. We present the BioInformatics WalkThrough (BIWT) software to directly initialize spatial agent-based models from single-cell and spatial molecular data. We demonstrate how initialization strategies affect tumor-immune dynamics and spatial clustering, positioning BIWT as a software suite to generate data-driven virtual cells representing both experimental and clinical contexts. AVAILABILITY AND IMPLEMENTATION: The BIWT software is available at https://github.com/PhysiCell-Tools/PhysiCell-Studio. The sample dataset for running the BIWT is available at https://zenodo.org/records/16365625. The code and instructions for reproducing the use case example is available at https://github.com/drbergman/BIWT-Paper.

Software↗

Significance analysis of lexical bias in microarray data.

BACKGROUND: Genes that are determined to be significantly differentially regulated in microarray analyses often appear to have functional commonalities, such as being components of the same biochemical pathway. This results in certain words being under- or overrepresented in the list of genes. Distinguishing between biologically meaningful trends and artifacts of annotation and analysis procedures is of the utmost importance, as only true biological trends are of interest for further experimentation. A number of sophisticated methods for identification of significant lexical trends are currently available, but these methods are generally too cumbersome for practical use by most microarray users. RESULTS: We have developed a tool, LACK, for calculating the statistical significance of apparent lexical bias in microarray datasets. The frequency of a user-specified list of search terms in a list of genes which are differentially regulated is assessed for statistical significance by comparison to randomly generated datasets. The simplicity of the input files and user interface targets the average microarray user who wishes to have a statistical measure of apparent lexical trends in analyzed datasets without the need for bioinformatics skills. The software is available as Perl source or a Windows executable. CONCLUSION: We have used LACK in our laboratory to generate biological hypotheses based on our microarray data. We demonstrate the program's utility using an example in which we confirm significant upregulation of SPI-2 pathogenicity island of Salmonella enterica serovar Typhimurium by the cation chelator dipyridyl.

2,2'-Dipyridyl↗

[In silicon cloning of HV126, a novel human gene related to multi drug resistance in leukemia].

OBJECTIVE: To find the novel gene related to the multi-drug resistance in leukemia and explore the molecular mechanism of multi-drug resistance. METHODS: The subtracted HL-60/VCR cDNA library was generated through the suppression subtractive hybridization using the wild HL-60 cells' cDNA as target and HL-60/ ATRA cells' as driver. A novel expression sequence tag (EST) sequence, which differentially expressed in HL-60/ ATRA cell, was screened by cDNA chip. Then a novel human gene, HV126 was assembled by the EST assembly tools. Bioinformatical databases and softwares were used to analyze and predict its function. Reverse transcription-PCR (RT-PCR) was used to detect the expression of HV-126 gene in leukemia cells before and after chemotherapy. RESULTS: The full open reading frames (ORFs) of the novel EST assembled by overlapping dbEST sequences included a 1991 bp nucleic sequence, which was named HV126. The deduced amino acid sequence consisted of 365 amino acids. The sequence of the novel gene exhibited 43% homology to a known gene, which is a possible member of the death domain-flood family implicated in apoptosis and inflammation. The expression of HV126 was proved to be related to the drug sensitivity in leukemia cells by RT-PCR. CONCLUSION: HV126, the novel gene, might have roles in regulating multi-drug resistance in leukemia. Further laboratory research should be done on cloning and making clear the gene function.

Antineoplastic Agents↗

PROMPT: a protein mapping and comparison tool.

BACKGROUND: Comparison of large protein datasets has become a standard task in bioinformatics. Typically researchers wish to know whether one group of proteins is significantly enriched in certain annotation attributes or sequence properties compared to another group, and whether this enrichment is statistically significant. In order to conduct such comparisons it is often required to integrate molecular sequence data and experimental information from disparate incompatible sources. While many specialized programs exist for comparisons of this kind in individual problem domains, such as expression data analysis, no generic software solution capable of addressing a wide spectrum of routine tasks in comparative proteomics is currently available. RESULTS: PROMPT is a comprehensive bioinformatics software environment which enables the user to compare arbitrary protein sequence sets, revealing statistically significant differences in their annotation features. It allows automatic retrieval and integration of data from a multitude of molecular biological databases as well as from a custom XML format. Similarity-based mapping of sequence IDs makes it possible to link experimental information obtained from different sources despite discrepancies in gene identifiers and minor sequence variation. PROMPT provides a full set of statistical procedures to address the following four use cases: i) comparison of the frequencies of categorical annotations between two sets, ii) enrichment of nominal features in one set with respect to another one, iii) comparison of numeric distributions, and iv) correlation of numeric variables. Analysis results can be visualized in the form of plots and spreadsheets and exported in various formats, including Microsoft Excel. CONCLUSION: PROMPT is a versatile, platform-independent, easily expandable, stand-alone application designed to be a practical workhorse in analysing and mining protein sequences and associated annotation. The availability of the Java Application Programming Interface and scripting capabilities on one hand, and the intuitive Graphical User Interface with context-sensitive help system on the other, make it equally accessible to professional bioinformaticians and biologically-oriented users. PROMPT is freely available for academic users from http://webclu.bio.wzw.tum.de/prompt/.

Computational Biology↗

Bioinformatics.

Computer databases, networks and software tools are essential materials and methods for biomedical research and are involved in almost every aspect of disease gene mapping and positional cloning. Public databases of DNA and protein sequences and genetic and physical map information are increasing rapidly in size and complexity and are also improving in quality, comprehensiveness, interoperability and access. A new generation of software tools for navigating through the biomedical literature has become available. Programs for sequence homology searching and genetic map construction have become more sophisticated, yet easier to use. Global computer networks are bringing state-of-the-art capabilities to all.

Chromosome Mapping↗

STING Millennium Suite: integrated software for extensive analyses of 3d structures of proteins and their complexes.

BACKGROUND: The integration of many aspects of protein/DNA structure analysis is an important requirement for software products in general area of structural bioinformatics. In fact, there are too few software packages on the internet which can be described as successful in this respect. We might say that what is still missing is publicly available, web based software for interactive analysis of the sequence/structure/function of proteins and their complexes with DNA and ligands. Some of existing software packages do have certain level of integration and do offer analysis of several structure related parameters, however not to the extent generally demanded by a user. RESULTS: We are reporting here about new Sting Millennium Suite (SMS) version which is fully accessible (including for local files at client end), web based software for molecular structure and sequence/structure/function analysis. The new SMS client version is now operational also on Linux boxes and it works with non-public pdb formatted files (structures not deposited at the RCSB/PDB), eliminating earlier requirement for the registration if SMS components were to be used with user's local files. At the same time the new SMS offers some important additions and improvements such as link to ProTherm as well as significant re-engineering of SMS component ConSSeq. Also, we have added 3 new SMS mirror sites to existing network of global SMS servers: Argentina, Japan and Spain. CONCLUSION: SMS is already established software package and many key data base and software servers worldwide, do offer either a link to, or host the SMS. SMS (Sting Millennium Suite) is web-based publicly available software developed to aid researches in their quest for translating information about the structures of macromolecules into knowledge. SMS allows to a user to interactively analyze molecular structures, cross-referencing visualized information with a correlated one, available across the internet. SMS is already used as a didactic tool by some universities. SMS analysis is now possible on Linux OS boxes and with no requirement for registration when using local files.

Algorithms↗

APBioNet: the Asia-Pacific regional consortium for bioinformatics.

Bioinformatics and computational biology, along with the related fields of genomics, proteomics, functional genomics and systems biology are new wave scientific disciplines that harness composite computational power across networks to advance biological knowledge at the most basic level and to direct traditional laboratory-based research efforts in the biomedical sciences. 'Fostering the growth of bioinformatics and allied disciplines in the Asia-Pacific region' is the motto of the first regional bioinformatics society, the Asia-Pacific Bioinformatics Network (APBioNet). APBioNet addresses the issues of hardware, software, databases and networks pertaining to bioinformatics, with the additional layer of pertinent education, training and research. Recent milestones achieved include hosting an international bioinformatics symposium in Asia and setting up large-scale regional grid-computing projects.

Asia↗

XML schemas for common bioinformatic data types and their application in workflow systems.

BACKGROUND: Today, there is a growing need in bioinformatics to combine available software tools into chains, thus building complex applications from existing single-task tools. To create such workflows, the tools involved have to be able to work with each other's data--therefore, a common set of well-defined data formats is needed. Unfortunately, current bioinformatic tools use a great variety of heterogeneous formats. RESULTS: Acknowledging the need for common formats, the Helmholtz Open BioInformatics Technology network (HOBIT) identified several basic data types used in bioinformatics and developed appropriate format descriptions, formally defined by XML schemas, and incorporated them in a Java library (BioDOM). These schemas currently cover sequence, sequence alignment, RNA secondary structure and RNA secondary structure alignment formats in a form that is independent of any specific program, thus enabling seamless interoperation of different tools. All XML formats are available at http://bioschemas.sourceforge.net, the BioDOM library can be obtained at http://biodom.sourceforge.net. CONCLUSION: The HOBIT XML schemas and the BioDOM library simplify adding XML support to newly created and existing bioinformatic tools, enabling these tools to interoperate seamlessly in workflow scenarios.

Algorithms↗

BioArray Software Environment (BASE): a platform for comprehensive management and analysis of microarray data.

The microarray technique requires the organization and analysis of vast amounts of data. These data include information about the samples hybridized, the hybridization images and their extracted data matrices, and information about the physical array, the features and reporter molecules. We present a web-based customizable bioinformatics solution called BioArray Software Environment (BASE) for the management and analysis of all areas of microarray experimentation. All software necessary to run a local server is freely available.

Database Management Systems↗

MutaProt: a web interface for structural analysis of point mutations.

A web-based tool, termed 'MutaProt', is described which analyses pairs of PDB files whose members differ in one, or two, amino acids. MutaProt examines the micro environment surrounding the exchanged residue(s) and can be searched by specifying a PDB ID, keywords, or any pair of amino acids. Detailed information about accessibility of the exchanged residue(s) and its atomic contacts are provided based on CSU software (Sobolev et al., Bioinformatics, 15, 327-332, 1999). An interactive 3D presentation of the superimposed regions around the mutation(s) is included. MutaProt is updated weekly.

Databases, Factual↗

Bioinformatics for rice resources.

The distinguishing feature of the 'new biology' is that it is information intensive. Not only does it demand access to and assimilation of vast data sets accumulated by engineered laboratory processes, but it also demands a previously unimaginable level of data integration across data types and sources. There are various information resources available for rice. In addition, there are various information resources that are not focused on rice but that contain rice data. The challenge for rice researchers and breeders is to access this wealth of data meaningfully. This challenge will grow significantly as international efforts aimed at sequencing the entire rice genome come into full swing. Only through concerted efforts in bioinformatics will the power of these public data be brought to bear on the needs of rice researchers and breeders worldwide. These efforts will need to focus on two large but distinct areas: (1) development of an effective bioinformatics infrastructure (hardware systems, software systems, and software engineers and support staff) and (2) computational biology research in visualization and analysis of very large, complex data sets, such as those that will be developed using high-throughput expression technologies, large-scale insertional mutagenesis, and biochemical profiling of various types. In the midst of the large flow of high-throughput data that the international rice genome sequencing efforts will produce, it is also imperative that integration of those data with unique germplasm data held in trust by the CGIAR be a part of the informatics infrastructure. This paper will focus on the state of rice information resources, the needs of the rice community, and some proposed bioinformatics activities to support these needs.

Algorithms↗