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Biomedical informatics for proteomics.

Success in proteomics depends upon careful study design and high-quality biological samples. Advanced information technologies, and also an ability to use existing knowledge to the full, will be crucial in making sense of the data. Despite its genome-scale potential, proteome analysis is at a much earlier stage of development than genomics and gene expression (microarray) studies. Fundamental issues involving biological variability, pre-analytic factors and analytical reproducibility remain to be resolved. Consequently, the analysis of proteomics data is currently informal and relies heavily on expert opinion. Databases and software tools developed for the analysis of molecular sequences and microarrays are helpful, but are limited owing to the unique attributes of proteomics data and differing research goals.

Biomedical Research↗

Online identification of viruses.

A computerized animal virus information system is developed in the Sequence Retrieval System (SRS) format. This database is available on the Word Wide Web (WWW) at the site http://bioinfo.ernet.in/www/avis/avis++ +.html. The database has been used to generate large number of identification matrices for each family. The software is developed in C. Unix shell scripts and Hypertext Marked-up Language (HTML) to assign the family to an unknown virus deterministically and to identify the virus probabilistically. It has been shown that such web based virus identification approach provides results with high confidence in those cases where identification matrix uses large number of independent characters. Protein sequence data for animal viruses have been analyzed and oligopeptides specific to each virus family and also specific to each virus species are identified for several viruses. These peptides thus could be used to identify the virus and to assign the virus family with high confidence showing the usefulness of sequence data in virus identification.

Databases as Topic↗

First year's experience of the MAClinical Computer Workstations Project.

We have an installed base of MAClinical workstations available on hospital wards, which have been used for patient care, education, and research 24 hours a day for the past year. We began with eight machines in the hospital but now have distributed ten more machines to faculty. We have recently increased the programming staff so we can develop more software. The machines and their installation were costly, but have already proven useful for teaching and patient care. Plans for the second and third years of the MAClinical project include workstations for the faculty coordinators of clinical clerkships and expansion of workstations to affiliated hospitals where our students and residents rotate. Software will be expanded to include patient simulations and expert consultations. Medical practice, research, and teaching in the future will need to make more use of information technology. It is not yet clear exactly how and where computers will best serve clinical medicine, but the teaching hospital can be both a laboratory for developing applications and a school for training physicians to use them.

Clinical Clerkship↗

Annular phased-array high-intensity focused ultrasound device for image-guided therapy of uterine fibroids.

An ultrasound (US), image-guided high-intensity focused ultrasound (HIFU) device was developed for noninvasive ablation of uterine fibroids. The HIFU device was an annular phased array, with a focal depth range of 30-60 mm, a natural focus of 50 mm, and a resonant frequency of 3 MHz. The in-house control software was developed to operate the HIFU electronics drive system for inducing tissue coagulation at different distances from the array. A novel imaging algorithm was developed to minimize the HIFU-induced noise in the US images. The device was able to produce lesions in bovine serum albumin-embedded polyacrylamide gels and excised pig liver. The lesions could be seen on the US images as hyperechoic regions. Depths ranging from 30 to 60 mm were sonicated at acoustic intensities of 4100 and 6100 W/cm2 for 15 s each, with the latter producing average lesion volumes at least 63% larger than the former. Tissue sonication patterns that began distal to the transducer produced longer lesions than those that began proximally. The variation in lesion dimensions indicates the possible development of HIFU protocols that increase HIFU throughput and shorten tumor treatment times.

Algorithms↗

User stress detection in human-computer interactions.

The emerging research area of Affective Computing seeks to advance the field of Human-Computer Interaction (HCI) by enabling computers to interact with users in ways appropriate to their affective states. Affect recognition, including the use of psychophysiologcal measures (e.g. heart rate), facial expressions, speech recognition etc. to derive an assessment of user affective state based on factors from the current task context, is an important foundation required for the development of Affective Computing. Our research focuses on the use of three physiological signals: Blood Volume Pulse (BVP), Galvanic Skin Response (GSR) and Pupil Diameter (PD), to automatically monitor the level of stress in computer users. This paper reports on the hardware and software instrumentation development and signal processing approach used to detect the stress level of a subject interacting with a computer, within the framework of a specific experimental task, which is called the 'Stroop Test'. For this experiment, a computer game was implemented and adapted to make the subject experience the Stroop Effect, evoked by the mismatch between the font color and the meaning of a certain word (name of a color) displayed, while his/her BVP, GSR and PD signals were continuously recorded. Several data processing techniques were applied to extract effective attributes of the stress level of the subjects throughout the experiment. Current results indicate that there exists interesting similarity among changes in those three signals and the shift in the emotional states when stress stimuli are applied to the interaction environment.

Adult↗

DINAMelt web server for nucleic acid melting prediction.

The DINAMelt web server simulates the melting of one or two single-stranded nucleic acids in solution. The goal is to predict not just a melting temperature for a hybridized pair of nucleic acids, but entire equilibrium melting profiles as a function of temperature. The two molecules are not required to be complementary, nor must the two strand concentrations be equal. Competition among different molecular species is automatically taken into account. Calculations consider not only the heterodimer, but also the two possible homodimers, as well as the folding of each single-stranded molecule. For each of these five molecular species, free energies are computed by summing Boltzmann factors over every possible hybridized or folded state. For temperatures within a user-specified range, calculations predict species mole fractions together with the free energy, enthalpy, entropy and heat capacity of the ensemble. Ultraviolet (UV) absorbance at 260 nm is simulated using published extinction coefficients and computed base pair probabilities. All results are available as text files and plots are provided for species concentrations, heat capacity and UV absorbance versus temperature. This server is connected to an active research program and should evolve as new theory and software are developed. The server URL is http://www.bioinfo.rpi.edu/applications/hybrid/.

Algorithms↗

The Colposcopy Clinic Data System.

Microcomputers are well suited to general data management, yet applications have not been available to meet the highly specialized requirements of a colposcopy clinic. Software was developed under the hypothesis that a specifically tailored application could improve the quality of patient care and facilitate medical education.

Colposcopy↗

Semi-automatic analysis of unit channel conductance from voltage ramp records.

An IBM PC-compatible computer program, RAMP, for evaluation of single-channel recordings acquired using voltage ramp protocols is presented. The program uses semi-automatic procedures to make necessary corrections to a record (e.g. subtraction of baseline shift) and to measure all channel slope conductances as well as reversal potentials. The output is either a hardcopy of graphic display, which includes the calculated parameters, or data in ASCII format for further use (e.g. plots using various graphic software). Originally, the software was developed for the evaluation of voltage ramp records of single channel data from maxi chloride channels in myoblasts of a muscle cell line (Hurnák and Zachar 1992). Records from these membrane patches were also used in this work to demonstrate basic principles of the software and its practical use in evaluating single channel records obtained in response to the application of voltage ramps. The channel conductances calculated from ramp records were compared with those obtained by classical evaluation procedures from voltage step records.

Animals↗

Software for primary healthcare in a developing country. Background and problem statement.

Nurses in primary healthcare (PHC) clinics carry a heavy administrative burden, much of which can be computerized. Advantages and disadvantages of computerization and issues related to patient records and other requirements of computerized systems are well documented. However, not much attention has been given to users' needs in PHC environments in developing countries. Users in township areas have very specific needs because of a lack of previous exposure to computers and a reluctance to change working habits. Some general software requirements that system developers should consider are discussed.

Attitude of Health Personnel↗

A method for the prediction of GPCRs coupling specificity to G-proteins using refined profile Hidden Markov Models.

BACKGROUND: G- Protein coupled receptors (GPCRs) comprise the largest group of eukaryotic cell surface receptors with great pharmacological interest. A broad range of native ligands interact and activate GPCRs, leading to signal transduction within cells. Most of these responses are mediated through the interaction of GPCRs with heterotrimeric GTP-binding proteins (G-proteins). Due to the information explosion in biological sequence databases, the development of software algorithms that could predict properties of GPCRs is important. Experimental data reported in the literature suggest that heterotrimeric G-proteins interact with parts of the activated receptor at the transmembrane helix-intracellular loop interface. Utilizing this information and membrane topology information, we have developed an intensive exploratory approach to generate a refined library of statistical models (Hidden Markov Models) that predict the coupling preference of GPCRs to heterotrimeric G-proteins. The method predicts the coupling preferences of GPCRs to Gs, Gi/o and Gq/11, but not G12/13 subfamilies. RESULTS: Using a dataset of 282 GPCR sequences of known coupling preference to G-proteins and adopting a five-fold cross-validation procedure, the method yielded an 89.7% correct classification rate. In a validation set comprised of all receptor sequences that are species homologues to GPCRs with known coupling preferences, excluding the sequences used to train the models, our method yields a correct classification rate of 91.0%. Furthermore, promiscuous coupling properties were correctly predicted for 6 of the 24 GPCRs that are known to interact with more than one subfamily of G-proteins. CONCLUSION: Our method demonstrates high correct classification rate. Unlike previously published methods performing the same task, it does not require any transmembrane topology prediction in a preceding step. A web-server for the prediction of GPCRs coupling specificity to G-proteins available for non-commercial users is located at http://bioinformatics.biol.uoa.gr/PRED-COUPLE.

Algorithms↗

Educational software evaluation process.

The Active Digital Library at the Vanderbilt University Medical Center has created and implemented an educational software evaluation process to facilitate the timely recommendation for product acquisition. Using this process, breadth and depth of subject coverage, clarity of presentation, quality of construction, and ease of use are being assessed by content and technical experts. The process uses a team approach, employing a bi-level evaluation instrument based on existing software evaluation forms and system bug reports.

Computer-Assisted Instruction↗

The object technology framework: an object-oriented interface to molecular data and its application to collagen.

We describe the Object Technology Framework (OTF) software system developed at the University of California, San Francisco Computer Graphics Laboratory for creating C+2 classes that facilitate rapid biomolecular application development and the application of the OTF to collagen modeling. C+2 class libraries for accessing and manipulating data from standard scientific data sources can be generated using the program genlib and its class library toolkit Molecule, thereby facilitating development of new applications. Use of the OTF for generating ideal collagen structural models (gencollagen) is described. The source code for the OTF is freely available at http:/(/)www.cgl.ucsf.edu/off/ to interested application developers.

Collagen↗

A new methodology for the measurement of the Wiberg angle in infants under 3 months.

This article describes the measurement of the Wiberg center edge angle in infants under 3 months using sonographic images of their hips. In the literature review, there was no reference of the application of this angle in this particular age group. Thus, a methodology has been developed based upon the fact that, at this age, the acetabular roof constitutes a large portion of hyaline cartilage. In this way, it was concluded that it was not possible to apply the original Wiberg method since the center of the femoral head can be only estimated and not accurately determined in plain radiography. For this present study, 400 hips of 200 infants were analyzed. All these hips were classified as type 1a or 1b, according to Graf. The sonographic images were transferred to a Pentium computer through a video Spigot interface. The images were analyzed by software specially developed for this purpose. Since ultrasonography allows the exact recognition of the anatomical elements of the hip joint in young children, software provided the acetabular cartilaginous roof angle that corresponds to the center edge angle in adults. The authors believe that this method will be helpful in the early detection of morphological alterations in the hip joint.

Cadaver↗

Transformation and average as handy tools for pressure measurement data analysis.

INTRODUCTION:: Pressure measurement data underneath[Table: see text] the foot represent usually a large number of data files which is equal to double product of the number of the subjects in study and of the number of the trials for each foot. Besides, 'normal' parameters are necessary to compare the results for the controls and for the subjects in study. Statistical parameters (mean values and standard deviations) are not very convenient when it is required to establish cartographical and geometrical parameters or peak pressures, maximum forces, contact areas, contact time and others for foot typing or as a standard. Sometimes it is reasonable to obtain average pressure data as a base for further data analysis. But taking into account that pressure distribution pattern may differ by its length, width and angle of the inclination of the foot axis to the horizontal it was necessary to solve a problem of transformation of any pressure picture to the given length and width (for vertical location of the foot axis). METHODS:: The transformed coordinates X(*) and Y(*) are defined from the following system of equations: X = Y(*) x width/width(*) x sina + X(*) x length/length(*) x cosa + X(o) Y = Y(*) x width/width(*) x cosa - X(*) x length/length(*) x sina + Y(o) where X(o), Y(o) -- the coordinates of the origin; width, length, a -- parameters of the initial pressure picture; width(*), length(*) -- parameters of the transformed pressure picture. X, Y -- are real values but the values of pressure are defined only in the integer coordinates. One of the main parts of average is a reduction of the time process to any number of frames. If N(max) is a maximum number of frames in one of the data files than all other data files must be transformed with accordance to the following formulas: for j-th frame the value of pressure for sensor with coordinates x, y is: P(*1)(xy) (j) = P(1)(xy) (i) x ki + P(1)(xy) (i+1) x k(i+1), where P(1)(xy) (i) -- pressure for sensor with coordinates x, y of the 1-th initial time process; j = 0, ellipsis, N(max) -1; j-th frame corresponds to i-th frame in the initial time process as i = integer(j) x (N -1)/(N(max) -1), N -- a number of frames in initial time process; coefficients k(i) and k(i+1) are equal to k(i) = j x (N -1)/(N(max) -1) -- I, k(i+1) = 1 - ki. Then the values of pressure are averaged: P(*)(xy) (j) = 1 / L x S P(1)(xy) (j), where L is a number of data files. Corresponding software was developed. RESULTS AND DISCUSSION:: 38 files of pressure measurement data of the teenagers from military school were chosen for transformation and average. Statistical errors of transformation and average were calculated for each data file (for peak pressure, force and area) and for all parameters from two software packages: Novel-win v.95.121 and Novel-ortho v.95.121. The maximum errors are for peak pressures (about 7%-10%) and contact areas (about 6%). CONCLUSION:: Transformation and average programs can be successfully used for data analysis additionally to traditional statistical software: groupmask evaluation program.

Journal Article↗

Localized current field hyperthermia in carcinoma of the cervix: 3-D computer simulation of SAR distribution.

Software was developed for the 3D simulation of SAR distribution for a 500 kHz localized current field hyperthermia system to be used in patients with carcinoma of the cervix. This hyperthermia system was specifically designed for use with a modified Fletcher-Suit intracavitary applicator. It consists of software modules for data input, tetrahedral grid generation and a numerical calculation of SAR distribution using an adaptive, multilevel finite element code. The AVS (Advanced Visual System, Inc.) system was used for the visual presentation of the results. A quasi-static approach was employed for the determination of SAR distribution. Results of the performed numerical tests were presented and they showed an important, clinically relevant ability to obtain a selective power deposition. This selective power deposition depended on the applicator geometry, i.e. the distance between the components of a Fletcher-Suit applicator and their relative position and the use of different modes of excitation.

Brachytherapy↗

Design, analysis, and implementation of a telemedicine remote consultation and diagnosis session playback using discrete event system specification.

Telemedicine remote consultation and diagnosis (RCD) software is a complex and distributed system. RCD allows physicians to collaborate on radiology or pathology cases from distributed geographic locations. It is very important to simplify design, construction, and maintenance of such a system. Currently, object-oriented design methodology is used to design and develop a software system in a modular fashion. Object-oriented software is made of various objects that work together. From the design of the software system, we get information about object methods and inheritance. We also get information about which objects are contained in a particular object and which objects are used by another object. One important element that the traditional object-oriented design misses is time. We propose the use of discrete event system specification (DEVS) in the design and analysis of a software system, such as RCD. With DEVS, coupling between objects can be specified explicitly and an object behavior can be shown in time. We introduce DEVS, show the time-line analysis of Remote Consultation and Diagnosis session playback using DEVS, and then describe its implementation.

Computer Communication Networks↗

[The x-ray cephalometric characteristics of the mesial bite in adults].

The purpose of the study was improving the quality of diagnosis and planning of treatment of adult patients with maxillodental abnormalities (mesial occlusion). A method for differential diagnosis of facial skull abnormalities was introduced, a modified scheme of x-ray cephalometric analysis was created, an automated diagnostic computer software was developed, forms of mesial occlusion were studied and described and their classification created. A total of 211 adult patients with mesial ratio of molars were examined. The principal method of examination was cephalometric analysis of the lateral teleroentgenograms of the skull using an original computer diagnostic software. Causes leading to formation of mesial occlusion were defined and classification of the abnormality offered.

Adolescent↗

SNPdetector: a software tool for sensitive and accurate SNP detection.

Identification of single nucleotide polymorphisms (SNPs) and mutations is important for the discovery of genetic predisposition to complex diseases. PCR resequencing is the method of choice for de novo SNP discovery. However, manual curation of putative SNPs has been a major bottleneck in the application of this method to high-throughput screening. Therefore it is critical to develop a more sensitive and accurate computational method for automated SNP detection. We developed a software tool, SNPdetector, for automated identification of SNPs and mutations in fluorescence-based resequencing reads. SNPdetector was designed to model the process of human visual inspection and has a very low false positive and false negative rate. We demonstrate the superior performance of SNPdetector in SNP and mutation analysis by comparing its results with those derived by human inspection, PolyPhred (a popular SNP detection tool), and independent genotype assays in three large-scale investigations. The first study identified and validated inter- and intra-subspecies variations in 4,650 traces of 25 inbred mouse strains that belong to either the Mus musculus species or the M. spretus species. Unexpected heterozygosity in CAST/Ei strain was observed in two out of 1,167 mouse SNPs. The second study identified 11,241 candidate SNPs in five ENCODE regions of the human genome covering 2.5 Mb of genomic sequence. Approximately 50% of the candidate SNPs were selected for experimental genotyping; the validation rate exceeded 95%. The third study detected ENU-induced mutations (at 0.04% allele frequency) in 64,896 traces of 1,236 zebra fish. Our analysis of three large and diverse test datasets demonstrated that SNPdetector is an effective tool for genome-scale research and for large-sample clinical studies. SNPdetector runs on Unix/Linux platform and is available publicly (http://lpg.nci.nih.gov).

Algorithms↗