Combinatorial codons: a computer program to approximate amino acid probabilities with biased nucleotide usage

Using techniques from optimization theory, we have developed a computer program that approximates a desired probability distribution for amino acids by imposing a probability distribution on the four nucleotides in each of the three codon positions. These base probabilities allow for the generation of biased codons for use in mutational studies and in the design of biologically encoded libraries. The dependencies between codons in the genetic code often makes the exact generation of the desired probability distribution for amino acids impossible. Compromises are often necessary. The program, therefore, not only solves for the "optimal" approximation to the desired distribution (where the definition of "optimal" is influenced by several types of parameters entered by the user), but also solves for a number of "sub-optimal" solutions that are classified into families of similar solutions. A representative of each family is presented to the program user, who can then choose the type of approximation that is best for the intended application. The Combinatorial Codons program is available for use over the web from http://www.wi.mit.edu/kim/computing.html.     

Beyond captions: linking figures with abstract sentences in biomedical articles

Although figures in scientific articles have high information content and concisely communicate many key research findings, they are currently under utilized by literature search and retrieval systems. Many systems ignore figures, and those that do not typically only consider caption text. This study describes and evaluates a fully automated approach for associating figures in the body of a biomedical article with sentences in its abstract. We use supervised methods to learn probabilistic language models, hidden Markov models, and conditional random fields for predicting associations between abstract sentences and figures. Three kinds of evidence are used: text in abstract sentences and figures, relative positions of sentences and figures, and the patterns of sentence/figure associations across an article. Each information source is shown to have predictive value, and models that use all kinds of evidence are more accurate than models that do not. Our most accurate method has an F1-score of 69% on a cross-validation experiment, is competitive with the accuracy of human experts, has significantly better predictive accuracy than state-of-the-art methods and enables users to access figures associated with an abstract sentence with an average of 1.82 fewer mouse clicks. A user evaluation shows that human users find our system beneficial. The system is available at http://FigureItOut.askHERMES.org.     

Automated preparation of DNA sequences for publication.

A computer program which draws DNA sequences is described. A simple method is used which enables the user to highlight or annotate specific parts of a sequence. The sizes of the characters in the sequence to be drawn are specified by the user. In addition, vertical spacing between lines and horizontal spacing between characters can be specified. Sequences can be prepared and high quality output produced on a plotter in a short period of time, making the program advantageous to use over typing, computer printing, or preparation by a graphics department.     

An interactive graphics program for comparing and aligning nucleic acid and amino acid sequences.

This paper describes a computer program designed to look for similarities between pairs of nucleic or amino acid sequences. The program looks both for segments of perfect identity or for regions where, using a scoring matrix, a minimum value is exceeded. The results of comparisons are presented as a matrix which is displayed on a simple graphics terminal. Use of a graphics terminal allows the user to display the whole of the two sequences in one screenful or to home-in on regions of interest to examine them in more detail. The program is interactive and so the user can easily see the effect of changes to variables and can use inbuilt editing functions to make insertions to produce alignments of the two sequences. These aligned sequences can then be saved on disk files for further processing.     

Multidimensional curve fitting program for biological data

A program written for use with the IBM-PC can be used to find least squares solutions to linearized multidimensional equations. The program is 'user-friendly' by requiring little from the user except to make decisions; most responses can be entered by a single keystroke. Once data are entered by the user, they can be repeatedly manipulated, graphed, and correlated. Many models relating data variables can be tried relatively easily, and best fit results found. Examples using respiratory mechanical data illustrate the ease of model comparisons.     

Resistance pattern of extended-spectrum beta-lactamase producing Enterobacteriaceae isolates

Gram-negative pathogens harboring extended-spectrum beta-lactamases (ESBL) are becoming an increasing therapeutic problem in many wards. The aim of our work was to study ESBL production by Enterobacteriaceae strains from Eastern Romania and their antimicrobial resistance. We selected 54 clinical isolates among 1068 enterobacteria according to their susceptibility spectrum (National Committee for Clinical Laboratory Standards, 1999). Antimicrobial susceptibility tests were performed using the Rapid ATB E gallery of mini API system (BioMérieux) and by a macrodilution method in Mueller-Hinton agar following standard procedure of the National Committee for Clinical Laboratory Standards (NCCLS). ESBL production was established by using both double disk synergy test (DDT) and Expert computer program of mini API. The isoelectric point (pI) was determined by isoelectric focusing in polyacrylamide gel and revealed by nitrocefin. As references we used beta-lactamases with known pI. The Expert computer program of mini API confirms the positive DDT test for all selected strains. Almost all strains displayed resistance to ampicillin, ampicillin/sulbactam or third generation cephalosporins and aztreonam. By IEF we identified 51 strains which have a unique enzyme. IEF pattern showed presence of two enzymes in three Escherichia coli strains. According to our results, the ESBL TEM-type are the most common for the studied isolates. The production of extended-spectrum beta-lactamases and the presence of the multiresistant of antimicrobial agents reflect, probably, the over use of third generation cephalosporins in Eastern Romania.     

A microcomputer based program for the storage and retrieval of experimental animal information

A microcomputer based program for the storage and selective retrieval of experimental animal information has been developed for use on any system which runs under CP/M system software. The program has been designed to be completely conversational, to communicate with the user in French, English, or Spanish, and to allow the user to define the data format and the alphanumeric coding scheme.     

GCI: A network server for interactive 3D graphics

The Graphics Command Interpreter (GCI) is an independent server module that can be interfaced to any program that needs interactive three-dimensional (3D) graphics capabilities. The principal advantage of GCI is its simplicity. Only a limited set of powerful features have been implemented, including object management, global and local transformations, rotation, translation, clipping, scaling, viewport operations, window management, menu handling and picking.GCI and the master (client) program it serves run concurrently, communicating over a local or remote TCP/IP network. GCI sets up socket communication and provides a 3D graphics window and a terminal emulator for the master program. Communication between the two programs is via ASCII strings over standard I/O channels. The implied language for messages is very simple. GCI interprets messages from the master program and implements them as changes of graphical objects or as text messages to the user. GCI provides the user with facilities to manipulate the view of the displayed 3D objects interactively, independently of the master program, and to communicate mouse-controlled selection of menu items or 3D points as well as keyboard strings to the master program.The program is written in C and initially implemented using the Silicon Graphics GL graphics library. As the need to link special libraries to the master program is completely avoided, GCI can very easily be interfaced to existing programs written in any language and running on any operating system capable of TCP/IP communication. The program is freely available.     

MixtureTree Annotator: A Program for Automatic Colorization and Visual Annotation of MixtureTree

The MixtureTree Annotator, written in JAVA, allows the user to automatically color any phylogenetic tree in Newick format generated from any phylogeny reconstruction program and output the Nexus file. By providing the ability to automatically color the tree by sequence name, the MixtureTree Annotator provides a unique advantage over any other programs which perform a similar function. In addition, the MixtureTree Annotator is the only package that can efficiently annotate the output produced by MixtureTree with mutation information and coalescent time information. In order to visualize the resulting output file, a modified version of FigTree is used. Certain popular methods, which lack good built-in visualization tools, for example, MEGA, Mesquite, PHY-FI, TreeView, treeGraph and Geneious, may give results with human errors due to either manually adding colors to each node or with other limitations, for example only using color based on a number, such as branch length, or by taxonomy. In addition to allowing the user to automatically color any given Newick tree by sequence name, the MixtureTree Annotator is the only method that allows the user to automatically annotate the resulting tree created by the MixtureTree program. The MixtureTree Annotator is fast and easy-to-use, while still allowing the user full control over the coloring and annotating process.     

Improving subcellular localization prediction using text classification and the gene ontology

MOTIVATION: Each protein performs its functions within some specific locations in a cell. This subcellular location is important for understanding protein function and for facilitating its purification. There are now many computational techniques for predicting location based on sequence analysis and database information from homologs. A few recent techniques use text from biological abstracts: our goal is to improve the prediction accuracy of such text-based techniques. We identify three techniques for improving text-based prediction: a rule for ambiguous abstract removal, a mechanism for using synonyms from the Gene Ontology (GO) and a mechanism for using the GO hierarchy to generalize terms. We show that these three techniques can significantly improve the accuracy of protein subcellular location predictors that use text extracted from PubMed abstracts whose references are recorded in Swiss-Prot.     

A minicomputer program for automatic saccade detection and linear analysis of eye movement systems using sine wave stimulus

A FORTRAN IV program is described, which may be run interactively or in batch and which allows a user to obtain the frequency response amplitude ratio and phase resulting from the linear analysis of an eye movement system using sine wave stimuli. The response (eye position) signal may contain components contributed by the saccadic eye movements. The program can digitize analog signals and store data on a magnetic tape. With the aid of digital filters, the program can detect saccades without requiring any input parameters from the user. The program interpolates the saccade interval using a method of least square curve fitting with a sine wave. The interpolation is relatively noise immune and works well regardless of the stimulus frequencies and the width of a saccade interval. Moreover, the program can handle long duration of signals such as 90 min of data which covers about 5 cycles of a 0.001 Hz sine wave signal. Sample runs for the cases of 0.001 and 0.1 Hz are given. The resident driver and the overlayable segments of the program have been implemented on a DEC (Digital Equipment Corp.) LAB-11 minicomputer (PDP 11/20).     

Automation of conformational analysis and other molecular modeling calculations

A software system has been developed for facilitating modeling calculations on large numbers of molecules. Using the system, it is possible to subject one or more molecules to a series of calculations, each requiring use of a different computer program. No user intervention is required: where necessary, output from one program is used automatically as input to the next. Names are assigned to output files automatically and in a systematic manner. As an example, the system can be used to perform a succession of calculations aimed at identifying the major low-energy conformers of each of a set of molecules, starting only from their chemical connectivities. The reliability of the results has been tested by calculations on 40 molecules taken from the Cambridge Structural Database. The observed crystal structure geometry could be found for the majority of these molecules.     

Methylation blockage and other improvements to a comprehensive DNA analysis program.

A comprehensive DNA analysis computer program was described in the second special issue of Nucleic Acids Research on the applications of computers to research on nucleic acids by Stone and Potter (1). Criteria used in designing the program were user friendliness, ability to handle large DNA sequences, low storage requirement, migratability to other computers and comprehensive analysis capability. The program has been used extensively in an industrial-research environment. This paper talks about improvements to that program. These improvements include testing for methylation blockage of restriction enzyme recognition sites, homology analysis, RNA folding analysis, integration of a large DNA database (GenBank), a site specific mutagenesis analysis, a protein database and protein searching programs. The original design of the DNA analysis program using a command executive from which any analytical programs can be called, has proven to be extremely versatile in integrating both developed and outside programs to the file management system employed.     

A flexible multiple sequence alignment program

The 'regions' method for multisequence alignment used in the previously reported program MALIGN has been generalized to include recursive refinement so that unaligned portions between two regions at the current level of resolution can be handled with increased resolution. Additionally, there is incorporated a limiting of the number of regions to be used at any level of resolution from which to abstract an alignment. This provides a significant increase in speed over the unlimited version. The program GENALIGN uses this improved regions method to execute fast pairwise alignments in the framework of Taylor's multisequence alignment procedure using clustered pairwise alignments. Pairwise alignments by dynamic programming are also provided in the program.     

A real-time and dynamic biological information retrieval and analysis system (BIRAS)

The aim of this study is to design a biological information retrieval and analysis system (BIRAS) based on the Internet. Using the specific network protocol, BIRAS system could send and receive information from the Entrez search and retrieval system maintained by National Center for Biotechnology Information (NCBI) in USA. The literatures, nucleotide sequence, protein sequences, and other resources according to the user-defined term could then be retrieved and sent to the user by pop up message or by E-mail informing automatically using BIRAS system. All the information retrieving and analyzing processes are done in real-time. As a robust system for intelligently and dynamically retrieving and analyzing on the user-defined information, it is believed that BIRAS would be extensively used to retrieve specific information from large amount of biological databases in now days. The program is available on request from the corresponding author.     

A protocol for the update of references to scientific literature in biological databases

Entries in biological databases are usually linked to scientific references. To generate those links and to keep them up-to-date, database maintainers have to continuously scan the scientific literature to select references that are relevant for each single database entry. The continuous growth of both the corpus of scientific literature and the size of biological databases makes this task very hard. We present a protocol intended to assist the updating of an existing set of literature (abstract) links from a single database entry with new references. It consists of taking the set of MEDLINE neighbour references of the existing linked abstracts and evaluating their relevance according to the existing set of abstracts. To test the applicability of the algorithm, we did a simple benchmark of the system using the references associated with the entries of a protein domain database. Human experts found the references that the algorithm scored highly were more relevant to the database entry than those scored lowly, suggesting that the algorithm was useful.     

Yale Image Finder (YIF): a new search engine for retrieving biomedical images

Yale Image Finder (YIF) is a publicly accessible search engine featuring a new way of retrieving biomedical images and associated papers based on the text carried inside the images. Image queries can also be issued against the image caption, as well as words in the associated paper abstract and title. A typical search scenario using YIF is as follows: a user provides few search keywords and the most relevant images are returned and presented in the form of thumbnails. Users can click on the image of interest to retrieve the high resolution image. In addition, the search engine will provide two types of related images: those that appear in the same paper, and those from other papers with similar image content. Retrieved images link back to their source papers, allowing users to find related papers starting with an image of interest. Currently, YIF has indexed over 140 000 images from over 34 000 open access biomedical journal papers. AVAILABILITY: http://krauthammerlab.med.yale.edu/imagefinder/     

PaperChase: a user-friendly program for searching the biomedical literature

PaperChase is a computer program which provides an efficient interface to the National Library of Medicine's MEDLINE database of references to the biomedical literature. The database includes references (citations) and abstracts compiled from Index Medicus, the International Nursing Index and the Index to Dental Literature. PaperChase may be accessed using any computer terminal or personal computer with modem. No special knowledge of computers or biomedical terms is necessary. Simple menus enable the novice to search the biomedical literature without training. A command language speeds searching for the experienced user. PaperChase does not require the user to know the database's indexing terminology, called Medical Subject Headings. Everyday language may be used and PaperChase will translate, or "map", the user's search term into the required Medical Subject Heading. PaperChase monitors a search in progress and suggests additional Medical Subject Headings which can be used to broaden or narrow a search. The searcher can order a full-text photocopy of any reference found in PaperChase. Support documentation and a subscriber newsletter are provided at no charge. Trained search specialists are available to offer assistance and to answer questions.     

Software for minimalistic data management in large camera trap studies

The use of camera traps is now widespread and their importance in wildlife studies is well understood. Camera trap studies can produce millions of photographs and there is a need for a software to help manage photographs efficiently. In this paper, we describe a software system that was built to successfully manage a large behavioral camera trap study that produced more than a million photographs. We describe the software architecture and the design decisions that shaped the evolution of the program over the study's three year period. The software system has the ability to automatically extract metadata from images, and add customized metadata to the images in a standardized format. The software system can be installed as a standalone application on popular operating systems. It is minimalistic, scalable and extendable so that it can be used by small teams or individual researchers for a broad variety of camera trap studies.