ORBIT: an integrated environment for user-customized bioinformatics tools

MOTIVATION: There are a large number of computational programs freely available to bioinformaticians via a client/server, web-based environment. However, the client interface to these tools (typically an html form page) cannot be customized from the client side as it is created by the service provider. The form page is usually generic enough to cater for a wide range of users. However, this implies that a user cannot set as 'default' advanced program parameters on the form or even customize the interface to his/her specific requirements or preferences. Currently, there is a lack of end-user interface environments that can be modified by the user when accessing computer programs available on a remote server running on an intranet or over the Internet. RESULTS: We have implemented a client/server system called ORBIT (Online Researcher's Bioinformatics Interface Tools) where individual clients can have interfaces created and customized to command-line-driven, server-side programs. Thus, Internet-based interfaces can be tailored to a user's specific bioinformatic needs. As interfaces are created on the client machine independent of the server, there can be different interfaces to the same server-side program to cater for different parameter settings. The interface customization is relatively quick (between 10 and 60 min) and all client interfaces are integrated into a single modular environment which will run on any computer platform supporting Java. The system has been developed to allow for a number of future enhancements and features. ORBIT represents an important advance in the way researchers gain access to bioinformatics tools on the Internet.     

Software Review of Risk*Assistant (Version 1.1) and RiskEZ (Version 1), both for Windows

RiskEZ and Risk*Assistant both make site risk assessment more accessible to many users and provide a relatively efficient means for performing screening level risk assessments. The programs perform basic site risk assessment calcu lations for users and provide point estimates of incremental individual cancer risks and non cancer hazard quotients following standard Environmental Pro tection Agency risk assessment guidance documents. Risk*Assistant allows the user to input raw data from which it can perform some dispersion modeling and calculate exposure point concentrations, while RiskEZ takes the exposure point concentrations as inputs. RiskEZ includes features that allow multiple network users to work on the same site and to deal with radioactive contami nants as well as chemical ones, while Risk*Assistant limits access to a site to one user at a time and it includes non radioactive substances. Neither program currently has the capability to perform probabilistic risk analyses, although Risk*Assistant allows the user to peform some sensitivity analysis. This review highlights differences between the programs and demonstrates how selection of a particular program might influence the results.     

INTROnSPECTIVE and NORA: computerized compositional characterization of regions within introns and around start codons on the basis of non-randomness analysis

Non-randomness analysis has recently proven a valuable method in the characterization of chromosomes and genomes with respect to the nucleotides around start codons. This methodology has been implemented in a distributable program NORA, which is presented as freeware for users in academia. Moreover, because the current knowledge about introns is limited, another application, INTROnSPECTIVE, has been developed. This application analyzes introns in either direction (from 5' to 3' or from 3' to 5') and the user has the option to exclude introns on the basis of their size or intron number within the gene. Both programs are based on initial parsing of GenBank flatfiles, i.e., with these programs, entire genomes or chromosomes can be parsed and characterized within seconds. The programs run under 32-bit Windows operating systems and can be obtained via . They are the only ones available which perform non-randomness analysis, and INTROnSPECTIVE represents a comprehensive and novel methodology for the study of introns.     

A Web Interface for Easy Flexible Protein-Protein Docking with ATTRACT

Protein-protein docking programs can give valuable insights into the structure of protein complexes in the absence of an experimental complex structure. Web interfaces can facilitate the use of docking programs by structural biologists. Here, we present an easy web interface for protein-protein docking with the ATTRACT program. While aimed at nonexpert users, the web interface still covers a considerable range of docking applications. The web interface supports systematic rigid-body protein docking with the ATTRACT coarse-grained force field, as well as various kinds of protein flexibility. The execution of a docking protocol takes up to a few hours on a standard desktop computer.     

Protein Structure Discovery: software package to perform computational proteomics tasks

Software-information system Protein Structure Discovery was developed. The system can be used for the wide range of tasks in the field of computer proteomics including prediction of function, structure and immunological properties of proteins. A specially created section of the system allows evaluating the quantitative and qualitative effects of mutations on the structural and functional properties of proteins. There are 19 of different programs integrated into the system, including the database of protein functional sites PDBSite, a PDBSiteScan program for the prediction of functional sites in three-dimensional structures of proteins, and WebProAnalyst program for the quantitative analysis of the structure-activity relationship of proteins. Protein Structure Discovery program has a Web interface and is available for users through the Internet (http://www-bionet.sscc.ru/psd/). For example, binding sites of zinc ion and ADP showed high stability of the method to errors PDBSiteScan reconstruction of spatial structures of proteins in the recognition of functional sites in model structures.     

Mprobe 2.0: computer-aided probe design for oligonucleotide microarray

DNA chips have proven to be effective tools in detecting gene expression levels. Compared with DNA chips using complementary DNA as probes, oligonucleotide microarrays using oligonucleotides as probes have attracted great attention because of their well known advantages. The design of gene-specific probes for each target is essential to the development of oligonucleotide microarrays. We have previously reported the development of a probe design software termed Mprobe 1.0. Here, we present a new version of this software, termed Mprobe 2.0. Several new features are included in Mprobe 2.0. Firstly, a paradox-based sequence database management system has been developed and integrated into the software, which consequently allows interoperability with sequences in GenBank, EMBL, and FASTA formats. Secondly, in contrast to setting a fixed threshold for the secondary structure of probes in Mprobe 1.0 and other related software, Mprobe 2.0 employs a different method. After parameters such as GC type, probe melting temperature and GC contents have been evaluated, candidate probes are sorted by the free energy from high to low value, followed by specificity analysis. Thirdly, Mprobe 2.0 provides users with substantial parameter options in the visual mode. Mprobe 2.0 possesses an easier interface for users to manage sequences annotated in different formats and design the optimal probes for oligonucleotide microarrays and other applications. AVAILABILITY: The program is free for non-commercial users and can be downloaded from the web page http://www.biosun.org.cn/mprobe/ CONTACT: Wuju Li (wujuli@yahoo.com or liwj@nic.bmi.ac.cn).     

CRISPR Primer Designer:Design primers for knockout and chromosome imaging CRISPR-Cas system

The clustered regularly interspaced short palin-dromic repeats (CRISPR)-associated system enables biologists to edit genomes precisely and provides a powerful tool for perturbing endogenous gene regula...     

Needle exchange programs: an economic evaluation of a local experience

OBJECTIVE: To determine whether providing a needle exchange program to prevent HIV transmission among injection drug users would cost less than the health care consequences of not having such a program. DESIGN: Incidence outcome model to estimate the number of cases of HIV infection that this program would prevent over 5 years, assuming that the HIV incidence rate would be 2% with the program and 4% without it, and that an estimated 275 injection drug users would use the service over this time. SETTING: Hamilton, Ont. OUTCOME MEASURES: Estimated number of cases of HIV infection expected to be prevented with and without the program over 5 years; estimated lifetime health care costs of treating an AIDS patient. The indirect costs of AIDS to society (e.g., lost productivity and informal caregiving) were not included. Projected costs were adjusted (discounted) to reflect their present value. In a sensitivity analysis, 3 parameters were varied: the estimate of the HIV transmission rate if no needle exchange program were provided, the number of injection drug users participating in the program, and the discount rate. RESULTS: With very conservative estimates, it was predicted that the Hamilton needle exchange program will prevent 24 cases of HIV infection over 5 years, thereby providing cost savings of $1.3 million after the program costs are taken into account. This translates into a ratio of cost savings to costs of 4:1. The sensitivity analysis confirmed that these findings are robust. CONCLUSION: Needle exchange programs are an efficient use of financial resources.     

Software Review of Distribution Fitting Programs: Crystal Ball and BestFit Add-In to @RISK

Simulation software programs continue to evolve and to meet the needs of risk analysts. In the past several years, two spreadsheet add-in programs added the capability of fitting distributions to data to their tool kits using classical statistical (i.e., non-Bayesian) methods. Crystal Ball version 4.0 now contains this capability in its standard program (and in Crystal Ball Pro version 4.0), while the BestFit software program is a component of the @RISK Decision Tools Suite that can also be purchased as a stand-alone program. Both programs will automatically fit distributions using maximum likelihood estimators to continuous data and provide goodness-of-fit statistics based on chi-squared, Kolmogorov-Smirnov, and Anderson-Darling tests. BestFit will also fit discrete distributions, and for all distributions it offers the option of optimizing the fit based on the goodness-of-fit parameters. Analysts should be wary of placing too much emphasis on the goodness-of-fit statistics given their limitations, and the fact that only some of the statistics are appropriately corrected to account for the fact that the distribution parameters are also fit using the data. These programs dramatically simplify efforts to use maximum likelihood estimation to fit distributions. However, the fact that a program is used to fit distributions should not be viewed as validation that the data have been fitted and interpreted correctly. Both programs rely heavily on the analyst's judgment and will allow analysts to fit inappropriate distributions. Currently, both programs could be improved by adding the ability to perform extensive basic exploratory data analysis and to give regression diagnostics that are needed to satisfy critical analysts or reviewers. Given that Bayesian methods are central to risk analysis, adding the capability of fitting distributions by combining data with prior information would greatly increase the utility of these programs.     

MD display: An interactive graphics program for visualization of molecular dynamics trajectories

MD Display was developed as a means of visualizing molecular dynamic trajectories generated by Amber.¹ The program runs on Silicon Graphics workstations, and features a simple user interface, and convenient display and analysis options. The program has now been extended to accept input from several other molecular dynamics programs.     

An access interface for the MS-DOS diskette format of GenBank(R), a gene sequence database

An interface program has been developed for users of MS-DOScomputers and the GenBank(R) gene sequence files in their disketteformat. With the program a user is able to produce keyword,author and entry name listings of GenBank items or to selectGenBank sequences for viewing, printing or decoding. The decodeoption uncompresses sequence data and yields a character filewhich has the format used on GenBank magnetic tapes. Programoptions are chosen by selecting items from command menus. Whilethe program is designed primarily for hard disk operation, italso allows users of diskette-based computers to work with GenBankfiles. Received on July 15, 1987; accepted on July 15, 1987     

SwissPIT: An workflow‐based platform for analyzing tandem‐MS spectra using the Grid

The identification and characterization of peptides from MS/MS data represents a critical aspect of proteomics. It has been the subject of extensive research in bioinformatics resulting in the generation of a fair number of identification software tools. Most often, only one program with a specific and unvarying set of parameters is selected for identifying proteins. Hence, a significant proportion of the experimental spectra do not match the peptide sequences in the screened database due to inappropriate parameters or scoring schemes. The Swiss protein identification toolbox (swissPIT) project provides the scientific community with an expandable multitool platform for automated in‐depth analysis of MS data also able to handle data from high‐throughput experiments. With swissPIT many problems have been solved: The missing standards for input and output formats (A), creation of analysis workflows (B), unified result visualization (C), and simplicity of the user interface (D). Currently, swissPIT supports four different programs implementing two different search strategies to identify MS/MS spectra. Conceived to handle the calculation‐intensive needs of each of the programs, swissPIT uses the distributed resources of a Swiss‐wide computer Grid (http://www.swing‐grid.ch).     

DNAssist: the integrated editing and analysis of molecular biology sequences in windows

MOTIVATION: The programs currently available for the analysis of nucleic acid and protein sequences suffer from a variety of problems: Web-based programs often require inconvenient reformatting of sequences when proceeding from one analysis to the next, and commercial-console-based programs are cost prohibitive. Here, we report the development of DNASSIST:, an inexpensive, multiple-document, interface program for the fully integrated editing and analysis of nucleic acid and protein sequences in the familiar environment of Microsoft Windows.