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PairWise and SearchWise: finding the optimal alignment in a simultaneous comparison of a protein profile against all DNA translation frames.

DNA translation frames can be disrupted for several reasons, including: (i) errors in sequence determination; (ii) RNA processing, such as intron removal and guide RNA editing; (iii) less commonly, polymerase frameshifting during transcription or ribosomal frameshifting during translation. Frameshifts frequently confound computational activities involving homologous sequences, such as database searches and inferences on structure, function or phylogeny made from multiple alignments. A dynamic alignment algorithm is reported here which compares a protein profile (a residue scoring matrix for one or more aligned sequences) against the three translation frames of a DNA strand, allowing frameshifting. The algorithm has been incorporated into a new package, WiseTools, for comparison of biological sequences. A protein profile can be compared against either a DNA sequence or a protein sequence. The program PairWise may be used interactively for alignment of any two sequence inputs. SearchWise can perform combinations of searches through DNA or protein databases by a protein profile or DNA sequence. Routine application of the programs has revealed a set of database entries with frameshifts caused by errors in sequence determination.

Algorithms↗

BTKbase, mutation database for X-linked agammaglobulinemia (XLA).

X-linked agammaglobulinemia (XLA) is an immunodeficiency caused by mutations in the gene coding for Bruton's agammaglobulinemia tyrosine kinase (BTK). A database (BTKbase) of BTK mutations has been compiled and the recent update lists 463 mutation entries from 406 unrelated families showing 303 unique molecular events. In addition to mutations, the database also lists variants or polymorphisms. Each patient is given a unique patient identity number (PIN). Information is included regarding the phenotype including symptoms. Mutations in all the five domains of BTK have been noticed to cause the disease, the most common event being missense mutations. The mutations appear almost uniformly throughout the molecule and frequently affect CpG sites that code for arginine residues. The putative structural implications of all the missense mutations are given in the database. The improved version of the registry having a number of new features is available at http://www. helsinki.fi/science/signal/btkbase.html

Agammaglobulinaemia Tyrosine Kinase↗

The SBASE domain library: a collection of annotated protein segments.

SBASE is a database of annotated protein domain sequences representing various structural, functional, ligand binding and topogenic segments of proteins. The current release of SBASE contains 27,211 entries which are provided with standardized names in order to facilitate retrieval. SBASE is cross-referenced to the major protein and nucleic acid databanks as well as to the PROSITE catalog of protein sequence patterns [Bairoch, A. (1992) Nucleic Acids Res., 20, Suppl., 2013-2118]. SBASE can be used to establish domain homologies through database search using programs such as FASTA [Lipman and Pearson (1985) Science, 227, 1436-1441], FASTDB [Brutlag et al. (1990) Comp. Appl. Biosci., 6, 237-245] or BLAST3 [Altschul and Lipman (1990) Proc. Natl. Acad. Sci. USA, 87, 5509-5513], which is especially useful in the case of loosely defined domain types for which efficient consensus patterns cannot be established. The use of SBASE is illustrated on the DNA binding protein Brain-4. The database and a set of search and retrieval tools are freely available on request to the authors or by anonymous 'ftp' file transfer from < ftp.icgeb.trieste.it >.

Amino Acid Sequence↗

SeqHelp: a program to analyze molecular sequences utilizing common computational resources.

Here we describe a tool to analyze molecular sequences utilizing the internet and existing computational resources for molecular biology. The computer program SeqHelp organizes information from database searches, gene structure prediction, and other information to generate multiply aligned, hypertext-linked reports to allow for fast analysis of molecular sequences. The efficient and economical strategy in this program can be employed to study molecular sequences for gene cloning, mutation analysis, and identical sequence search projects.

Algorithms↗

The SUPERFAMILY database in structural genomics.

The SUPERFAMILY hidden Markov model library representing all proteins of known structure predicts the domain architecture of protein sequences and classifies them at the SCOP superfamily level. This analysis has been carried out on all completely sequenced genomes. The ways in which the database can be useful to crystallographers is discussed, in particular with a view to high-throughput structure determination. The application of the SUPERFAMILY database to different target-selection strategies is suggested: novel folds, novel domain combinations and targeted attacks on genomes. Use of the database for more general inquiry in the context of structural studies is also explained. The database provides evolutionary relationships between target proteins and other proteins of known structure through the SCOP database, genome assignments and multiple sequence alignments.

Amino Acid Sequence↗

FastR: fast database search tool for non-coding RNA.

The discovery of novel non-coding RNAs has been among the most exciting recent developments in Biology. Yet, many more remain undiscovered. It has been hypothesized that there is in fact an abundance of functional non-coding RNA (ncRNA) with various catalytic and regulatory functions. Computational methods tailored specifically for ncRNA are being actively developed. As the inherent signal for ncRNA is weaker than that for protein coding genes, comparative methods offer the most promising approach, and are the subject of our research. We consider the following problem: Given an RNA sequence with a known secondary structure, efficiently compute all structural homologs (computed as a function of sequence and structural similarity) in a genomic database. Our approach, based on structural filters that eliminate a large portion of the database, while retaining the true homologs allows us to search a typical bacterial database in minutes on a standard PC, with high sensitivity and specificity. This is two orders of magnitude better than current available software for the problem.

Algorithms↗

Gene teams with relaxed proximity constraint.

Functionally related genes co-evolve, probably due to the strong selection pressure in evolution. Thus we expect that they are present in multiple genomes. Physical proximity among genes, known as gene team, is a very useful concept to discover functionally related genes in multiple genomes. However, there are also many gene sets that do not preserve physical proximity. In this paper, we generalized the gene team model, that looks for gene clusters in a physically clustered form, to multiple genome cases with relaxed constraint. We propose a novel hybrid pattern model that combines the set and the sequential pattern models. Our model searches for gene clusters with and/or without physical proximity constraint. This model is implemented and tested with 97 genomes (120 replicons). The result was analyzed to show the usefulness of our model. Especially, analysis of gene clusters that belong to B. subtilis and E. coli demonstrated that our model predicted many experimentally verified operons and functionally related clusters. Our program is fast enough to provide a sevice on the web at http://platcom. informatics.indiana.edu/platcom/. Users can select any combination of 97 genomes to predict gene teams.

Algorithms↗

PSIST: indexing protein structures using suffix trees.

Approaches for indexing proteins, and for fast and scalable searching for structures similar to a query structure have important applications such as protein structure and function prediction, protein classification and drug discovery. In this paper, we developed a new method for extracting the local feature vectors of protein structures. Each residue is represented by a triangle, and the correlation between a set of residues is described by the distances between Calpha atoms and the angles between the normals of planes in which the triangles lie. The normalized local feature vectors are indexed using a suffix tree. For all query segments, suffix trees can be used effectively to retrieve the maximal matches, which are then chained to obtain alignments with database proteins. Similar proteins are selected by their alignment score against the query. Our results shows classification accuracy up to 97.8% and 99.4% at the superfamily and class level according to the SCOP classification, and shows that on average 7.49 out of 10 proteins from the same superfamily are obtained among the top 10 matches. These results are competitive with the best previous methods.

Algorithms↗

Optimizing multiple seeds for protein homology search.

We present a framework for improving local protein alignment algorithms. Specifically, we discuss how to extend local protein aligners to use a collection of vector seeds or ungapped alignment seeds to reduce noise hits. We model picking a set of seed models as an integer programming problem and give algorithms to choose such a set of seeds. While the problem is NP-hard, and Quasi-NP-hard to approximate to within a logarithmic factor, it can be solved easily in practice. A good set of seeds we have chosen allows four to five times fewer false positive hits, while preserving essentially identical sensitivity as BLASTP.

Algorithms↗

Biomolecular optical data storage and data encryption.

The use of bacteriorhodopsin (BR) as an active layer in write-once-read-many optical storage is presented. This novel feature of BR materials may be used on a wide variety of substrates, among them transparent substrates but also paper and plastics. The physical basis of the recording process is polarization-sensitive two-photon absorption. As an example for this new BR application, an identification card equipped with an optical recording strip is presented, which has a capacity of about 1 MB of data. The recording density currently used is 125 kB/cm2, which is far from the optical limits but allows operation with cheap terminals using plastic optics. In the examples given, data are stored in blocks of 10 kB each. A special optical encryption procedure allows the stored data to be protected from unauthorized reading. The molecular basis of this property is again the polarization-sensitive recording mechanism. The unique combination of optical storage, photochromism, and traceability of the BR material is combined on the single-molecule level. BR introduces a new quality of storage capability for applications with increased security and anticounterfeiting requirements.

Bacteriorhodopsins↗

Lossy compression should not be used in certain imaging applications such as chest radiography. For the proposition.

Computational techniques are frequently used to compress image data so that transmission and storage requirements are reduced. If the computational techniques result in no loss in image resolution, the technique is referred to as lossless compression. Greater compression of data may yield some loss in spatial or temporal resolution, and is referred to as lossy compression. In some radiologic examinations [e.g., gastrointestinal (GI) studies], some resolution loss may be tolerable, whereas in others (chest examinations and mammography) it conceivably could result in missed pathology. Without lossy compression, however, data requirements can be overwhelming for transmission, storage and retrieval of images such as chest films. The unanswered question, addressed in this Point/Counterpoint issue, is whether some degree of lossy compression can be tolerated in chest radiography.

Humans↗

Effectiveness and efficiency of search methods in systematic reviews of complex evidence: audit of primary sources.

OBJECTIVE: To describe where papers come from in a systematic review of complex evidence. Method Audit of how the 495 primary sources for the review were originally identified. RESULTS: Only 30% of sources were obtained from the protocol defined at the outset of the study (that is, from the database and hand searches). Fifty one per cent were identified by "snowballing" (such as pursuing references of references), and 24% by personal knowledge or personal contacts. CONCLUSION: Systematic reviews of complex evidence cannot rely solely on protocol-driven search strategies.

Data Collection↗