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High speed homology search with FPGAs.

We will introduce a way how we can achieve high speed homology search by only adding one off-the-shelf PCI board with one Field Programmable Gate Array (FPGA) to a Pentium based computer system in use. FPGA is a reconfigurable device, and any kind of circuits, such as pattern matching program, can be realized in a moment. The performance is almost proportional to the size of FPGA which is used in the system, and FPGAs are becoming larger and larger following Moore's law. We can easily obtain latest/larger FPGAs in the form off-the-shelf PCI boards with FPGAs, at low costs. The result which we obtained is as follows. The performance is most comparable with small to middle class dedicated hardware systems when we use a board with one of the latest FPGAs and the performance can be furthermore accelerated by using more number of FPGA boards. The time for comparing a query sequence of 2,048 elements with a database sequence of 64 million elements by the Smith-Waterman algorithm is about 34 sec, which is about 330 times faster than a desktop computer with a 1 GHz Pentium III. We can also accelerate the performance of a laptop computer using a PC card with one smaller FPGA. The time for comparing a query sequence (1,024) with the database sequence (64 million) is about 185 sec, which is about 30 times faster than the desktop computer.

Computational Biology↗

Large-scale open bioinformatics data resources.

The data explosion in bioinformatics is relentless. More and more genomes are being sequenced and many new types of datasets are being generated in large-scale projects. Integration and true open access to the data are still difficult issues, although they are gradually being addressed. Notably, certain fields have good standardization and interoperability, while others lag behind. This review summarizes the latest developments in genome and sequences databases, transcriptomics data (ESTs, ORESTES, full-length cDNAs), proteomics data (protein databases, protein structures, family and domain classification) as well as loosely integrated fields, such as microarray experiments, mutation databases and databases of regulatory regions and elements. The review attempts to resist simply summarizing what data are available, and aims to provide a critical look at some of the integration and access issues associated with several of these resources.

Computational Biology↗

The need to embrace molecular profiling of tumor cells in prostate and bladder cancer.

PURPOSE: Current treatment strategies for urological cancer are still based on empirical formulae as opposed to treatment tailored for each cancer patient. To individualize treatment, the multiple molecular abnormalities within tumor cell populations needs to be mapped out. The aim of this article is to explain molecular profiling (MP) and its associated techniques so that the process is not purely seen as a research tool but as a future adjunctive measure in patient diagnosis and treatment. EXPERIMENTAL DESIGN: A Medline search of publications relating to MP of prostate and bladder cancer was carried out. A review article was written combining the relevant published literature along with the clinical and scientific experience of both centers. RESULTS: The advent of MP now provides a strategy by which these molecular abnormalities can be assessed. As well as being of diagnostic and prognostic use, these molecular profiles will identify putative molecular abnormalities within tumor cells that may be appropriate for therapeutic modulation. CONCLUSIONS: In prostate and bladder cancer, mapping out the molecular abnormalities could be translated into a valuable tool to help solve difficult issues regarding patient management decisions.

Gene Expression Regulation, Neoplastic↗

[Genetic characterization of the non-structural protein NSP4 from epidemic strains of human rotavirus in China].

BACKGROUND: To clarify the features of gene variation among epidemic strains of human rotavirus NSP4 in China. METHODS: SP4 genes from 27 epidemic strains of human rotavirus isolated in different area of China in recent years were amplified with RT-PCR, the resulted cDNAs were cloned and sequenced. The sequences of full length cDNAs were compared with 10 rotavirus NSP4 sequences available in the GenBank using the Clustal x 1.8 TreeView32 and DNA Star softwares. The G serotype of VP7 was analysed by PCR. RESULTS: The homology of the amino acid among the 27 rotavirus strains isolated in China was 81.7%-99.4%. Based on the variation of amino acid sequence, the virus strains can be divided into two groups, represented by Wa and KUN with the homology of 92.0%-99.4% and 92.0%-98.9% within each group, respectively. The diversity between the two groups were 16.6%-21.0%. The Wa group could further be separated into three subgroups, according to the diversity between those strains and the characterization in the highly variable domain. The association between VP7 serotype and NSP4 genotype was not strong. CONCLUSIONS: The NSP4 gene of human rotavirus epidemic strains in China can be divided into Wa and KUN two groups, Wa group is the main group and contains three subgroups possessing characteristic amino acid sites. Samples isolated in the same year but not in the same area shared higher homology.

Antigens, Viral↗

Identification and characterization of human ZPBP-like gene in silico.

PP1R1B-ERBB2-GRB7 locus on human chromo-some 17q12 is frequently amplified in gastric and breast cancer. Because recombination hot spot or fragile site is located around the terminus of amplified region (amplicon), we searched for a novel gene closely linked to the teromeric end of the ERBB2 amplicon. Here, we identified and characterized the ZPBP-like (ZPBPL) gene by using bioinformatics. ZPBPL gene, corresponding to BC043152 cDNA, was found to consist of seven exons. ZPBPL (316 aa) and ZPBP (351 aa) proteins, showing 34.8% total amino-acid identity, shared the zona pellucida binding protein homologous (ZPBH) domain with conserved 15 cysteine residues. ZPBPL was a secreted-type glycoprotein with the ZPBH domain, while ZPBP was a type 2 transmembrane protein with the extracellular ZPBH domain. ZPBPL mRNA was co-expressed with ZPBP mRNA in testis, germ cell tumor, and brain medulla. ZPBPL might be implicated in the gamete interaction during fertilization just like ZPBP. The MGC9753-ERBB2-MGC14832-GRB7-ZNFN1A3-ZPBPL-PRO2521-ORMDL3-GSDM locus on human chromosome 17q12-q21 and the ZPBP-ZNFN1A1-FIGNL1-DDC-GRB10-COBL-SEC61G-EGFR-LANCL2 locus on human chromosome 7p12-p11 were next compared. Comparative genomics revealed that ZPBPL-ZNFN1A3-GRB7-ERBB2 and ZPBP-ZNFN1A1-GRB10-EGFR loci were paralogous regions within the human genome. This is the first report on identification and characterization of the ZPBPL gene.

Amino Acid Sequence↗

[Therapeutic implications of advances in breast cancer biology].

The polygenic and multifactor genetic basis of breast cancer confers to each tumour a different phenotype and clinical outcome. A therapeutic stake is to better determine this heterogeneity by using more reliable prognostic factors and to develop molecular therapies targeting the tumour cells selectively. The study of molecular alterations in breast cancer allowed considerable therapeutic progress by use of the hormonal receptors and the ERBB2 receptor. Today, new high-throughput technologies such as DNA microarrays allow measuring the activity of thousands of genes in a sample simultaneously. The awaited repercussions are multiple. Expression profiling of breast tumours allows the identification of new sub-groups of tumour in groups a priori identical, but with different outcome. This stratification should make it possible to better tailor the treatment and boost the discovery of new therapeutic targets

Antineoplastic Agents, Hormonal↗

Detection of correlations in tRNA sequences with structural implications.

Using an flexible representation of biological sequences, we have performed a comparative analysis of 1208 known tRNA sequences. We believe we our technique is a more sensitive method for detecting structural and functional relationships in sets of aligned sequences because we use a flexible representation (for sequences), as well as a general statistical method that can detect a wide range of relationships between positions in a sequence. Our method utilizes functional classifications of the sequence building-blocks (nucleotide bases and amino acids) based on physical or chemical properties. This flexibility in sequence representation improves the significance of finding sequence relationships mediated by the defining property. For example, using a purine/pyrimidine classification, we can detect base-stacking interactions in sets of nucleotide sequences that form base-paired helices. We use several statistical measures, including chi 2-tests, Monte Carlo simulations and an information measure to detect significant correlations in sequences. In this paper we illustrate our method by analyzing a set of tRNA sequences and showing that the correlations our program discovers, in each case, correspond to the known base-pairing and higher order interactions observed in tRNA crystal structures. Furthermore, we show that novel and interesting features of tRNAs are detected when sequence correlations with the charged amino acid (and anticodon) are evaluated. This technique is a powerful method for predicting the structure of RNAs and for analyzing specific functional characteristics.

Base Composition↗

Molecular systematics of shrimp (Decapoda: Bresiliidae) from deep-sea hydrothermal vents, I: Enigmatic "small orange" shrimp from the Mid-Atlantic Ridge are juvenile Rimicaris exoculata.

Independent species descriptions of a "small orange" caridean shrimp found at deep-sea hydrothermal vents along the Mid-Atlantic Ridge have created the synonymous names Iorania concordia Vereshchaka 1996b and Rimicaris aurantiaca Martin et al. 1997. Our genetic analyses involving allozymes and mitochondrial DNA sequences reveal that the "small orange" shrimp described in these studies are a juvenile form of Rimicaris exoculata Williams and Rona, a species commonly found at these sites. In light of this result, we reconsider the life history and ecologic characteristics of juvenile and adult stages of Rimicaris exoculata.

Animals↗

Insights into a dinoflagellate genome through expressed sequence tag analysis.

BACKGROUND: Dinoflagellates are important marine primary producers and grazers and cause toxic "red tides". These taxa are characterized by many unique features such as immense genomes, the absence of nucleosomes, and photosynthetic organelles (plastids) that have been gained and lost multiple times. We generated EST sequences from non-normalized and normalized cDNA libraries from a culture of the toxic species Alexandrium tamarense to elucidate dinoflagellate evolution. Previous analyses of these data have clarified plastid origin and here we study the gene content, annotate the ESTs, and analyze the genes that are putatively involved in DNA packaging. RESULTS: Approximately 20% of the 6,723 unique (11,171 total 3'-reads) ESTs data could be annotated using Blast searches against GenBank. Several putative dinoflagellate-specific mRNAs were identified, including one novel plastid protein. Dinoflagellate genes, similar to other eukaryotes, have a high GC-content that is reflected in the amino acid codon usage. Highly represented transcripts include histone-like (HLP) and luciferin binding proteins and several genes occur in families that encode nearly identical proteins. We also identified rare transcripts encoding a predicted protein highly similar to histone H2A.X. We speculate this histone may be retained for its role in DNA double-strand break repair. CONCLUSION: This is the most extensive collection to date of ESTs from a toxic dinoflagellate. These data will be instrumental to future research to understand the unique and complex cell biology of these organisms and for potentially identifying the genes involved in toxin production.

Amino Acid Sequence↗

A deductive database system for analyzing human nucleotide sequence data.

The analysis of the human genome is one of the most significant topics in both biology and medical science. There is a growing need for a well-designed database system for searching and analyzing the human genome data. We developed a deductive database system to search and analyze nucleotide sequence data derived from the GenBank primates data. A deductive database system is a next generation one and it contains an inference mechanism that can handle problems beyond the capabilities of classical database systems. Database queries are described in logical rules. These rules are simple even for molecular biologists who are not experts in computer programs because they are declarative and do not require the procedural commands that are usually used in computer programs. Furthermore, queries based on logical rules are powerful enough to express complicated biological problems. Particularly, recursive rules are suitable for examining secondary structures of nucleotide sequences. In our analysis of TfR's IRE, we noted five stem-and-loop structures.

Artificial Intelligence↗

Biodiversity of organotin resistant Pseudomonas from west coast of India.

Five bacterial isolates were screened for resistance to organotin compound, i.e. tributyltin chloride (TBTC) up to 2 mM. The optimum pH, temperature and salinity for the growth of the isolates were found to be 7, 28 degrees C and 2.5%, respectively. The isolates were tested for survival tolerance to heavy metals (mercury, cadmium and zinc) and co-resistance to antibiotics viz. ampicillin, kanamycin, rifampicin, streptomycin, penicillin, chloramphenicol, tetracycline, nalidixic acid and neomycin. Although our earlier study reported that these five bacterial strains are of different species of Pseudomonas, our present 16S rRNA gene sequence analysis revealed that all the strains are Pseudomonas aeruginosa. One of five isolates P. aeruginosa strain 25W could grow in mineral salt medium with 2 mM of TBTC as a sole source of carbon and survive up to 5 mM of TBTC. In presence of 2 mM of TBTC there was comparable up-regulation of 45 kDa protein in the cell extract of the 25W isolate was found indicating involvement of certain enzymes in TBTC resistance.

Anti-Bacterial Agents↗

Selection of amino acid parameters for Fourier transform-based analysis of proteins.

Fourier analysis of the parametric profile of a sequence for the detection and localization of the structural motifs that are characteristic for biologically related proteins has been proposed. In order to select parameters that are most appropriate for this analysis, the informational capacity of 226 physicochemical, thermodynamic, structural and statistical amino acid parameters was analyzed. Based on the results, obtained for the four functionally unrelated protein model groups (lysozyme c, HIV-1 gp120, tubulin and tau proteins, and steroid hormone receptors), the electron-ion interaction potential has been selected as the unique amino acid property that can be used in Fourier transform-based analysis of proteins, independently of their biological function.

Acyl Carrier Protein↗

Universal sequence map (USM) of arbitrary discrete sequences.

BACKGROUND: For over a decade the idea of representing biological sequences in a continuous coordinate space has maintained its appeal but not been fully realized. The basic idea is that any sequence of symbols may define trajectories in the continuous space conserving all its statistical properties. Ideally, such a representation would allow scale independent sequence analysis--without the context of fixed memory length. A simple example would consist on being able to infer the homology between two sequences solely by comparing the coordinates of any two homologous units. RESULTS: We have successfully identified such an iterative function for bijective mapping psi of discrete sequences into objects of continuous state space that enable scale-independent sequence analysis. The technique, named Universal Sequence Mapping (USM), is applicable to sequences with an arbitrary length and arbitrary number of unique units and generates a representation where map distance estimates sequence similarity. The novel USM procedure is based on earlier work by these and other authors on the properties of Chaos Game Representation (CGR). The latter enables the representation of 4 unit type sequences (like DNA) as an order free Markov chain transition table. The properties of USM are illustrated with test data and can be verified for other data by using the accompanying web-based tool:http://bioinformatics.musc.edu/~jonas/usm/. CONCLUSIONS: USM is shown to enable a statistical mechanics approach to sequence analysis. The scale independent representation frees sequence analysis from the need to assume a memory length in the investigation of syntactic rules.

Algorithms↗