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共 371 条记录，以下是331-340 订阅

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Statistical issues in the analysis of the array CGH data

Statistical issues in the analysis of the array CGH data

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ieee conference on bioinformatics

作者： J. Fridlyand A. Snijders D. Pinkel D. Albertson Ajay Jain Comprehensive Cancer Center University of California San Francisco San Francisco CA USA

The development of solid tumors is associated with acquisition of complex genetic alterations, indicating that failures in the mechanisms that maintain the integrity of the genome contribute to tumor evolution. Thus, one expects that the particular types of genomic derangement seen in tumors reflect underlying failures in maintenance of genetic stability, as well as selection for changes that provide growth advantage. In order to investigate genomic alterations we are using microarray-based comparative genomic hybridization (array CGH). The computational task is to map and characterize the number and types of copy number alterations present in the tumors, and so define copy number phenotypes as well as to associate them with known biological markers. To utilize the spatial coherence between nearby clones, we use unsupervised Hidden Markov Models approach. The clones are partitioned into the states which represent underlying copy number of the group of clones. The method is demonstrated on the two cell line datasets with known copy number alterations for one of them. The biological conclusions drawn from the analyses are discussed.

关键词： Neoplasms Genomics bioinformatics Cloning Genetics Solids Evolution (biology) Stability Biology computing Biomarkers

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The sea urchin endomesoderm gene regulatory network, an encoded logic map for early development

The sea urchin endomesoderm gene regulatory network, an enco...

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ieee conference on bioinformatics

作者： E.H. Davidson California Institute of Technology Pasadena CA USA

The regulatory program for animal development is "wired" into the cis-regulatory networks of the genome. At the DNA level these networks consist of the clusters of cis-regulatory transcription factor target sites (modules) that direct the spatial and temporal expression of each phase of activity of those genes; and the linkages amongst them. Here "linkage" refers to the relation between genes encoding transcription factors and the target sites of genes which they control, and between the genes encoding elements of signal systems and their ultimate target genes. We are engaged in an effort to define at the genomic sequence level the gene regulatory network (GRN) controlling endomesoderm specification in sea urchin embryos. The proposed GRN is based on the following information: spatial and temporal expression patterns of all genes included; constraints from experimental embryology; and a massive perturbation analysis in which expression of every relevant gene is perturbed and the effects on all other genes measured. The GRN consists of predicted inputs into the cis-regulatory modules controlling the endomesoderm expression of the genes involved. These predictions can be tested at the cis-regulatory level: here several such tests are presented. They show that the perturbation analysis is a surprisingly informative predictor of DNA sequence-level regulatory transactions.

关键词： Logic Genomics bioinformatics DNA Couplings Encoding Embryo Testing Animals Control systems

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Fast and accurate probe selection algorithm for large genomes

Fast and accurate probe selection algorithm for large genome...

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ieee conference on bioinformatics

作者： W.-K. Sung W.-H. Lee Department of Computer Science National University of Singapore Singapore Genome Institute of Singapore Singapore

The oligo microarray (DNA chip) technology in recent years has a significant impact on genomic study. Many fields such as gene discovery, drug discovery, toxicological research and disease diagnosis, will certainly benefit from its use. A microarray is an orderly arrangement of thousands of DNA fragments where each DNA fragment is a probe (or a fingerprint) of a gene/cDNA. It is important that each probe must uniquely associate with a particular gene/cDNA. Otherwise, the performance of the microarray will be affected. Existing algorithms usually select probes using the criteria of homogeneity, sensitivity, and specificity. Moreover, they improve efficiency employing some heuristics. Such approaches reduce the accuracy. Instead, we make use of some smart filtering techniques to avoid redundant computation while maintaining the accuracy. Based on the new algorithm, optimal short (20 bases) or long (50 or 70 bases) probes can be computed efficiently for large genomes.

关键词： Probes Genomics bioinformatics DNA Pharmaceutical technology Drugs Toxicology Diseases Fingerprint recognition Filtering

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Automatic recognition of regions of intrinsically poor multiple alignment using machine learning

Automatic recognition of regions of intrinsically poor multi...

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ieee conference on bioinformatics

作者： Y. Shan E.E. Milios A.J. Roger C. Blouin E. Susko Faculty of Computer Science Dalhousie University Halifax NS Canada Department of Biochemistry and Molecular Biology Genome Atlantic Genome Canada Dalhousie University Halifax NS Canada Department of Mathematics and Statistics Dalhousie University Halifax NS Canada

Phylogenetic analysis requires alignment of gene or protein sequences. Some regions of genes evolve fast and suffer numerous insertion and deletion events and cannot be aligned reliably with automatic alignment algorithms. Such regions of intrinsically uncertain alignment are currently detected and deleted manually before performing phylogenetic analysis. We present the results of a machine learning approach to detect regions of poor alignment automatically. We compare the results obtained from Naive Bayes (NB), C4.5 decision tree (C4.5) and support vector machine (SVM) approaches.

关键词： Machine learning Support vector machines Support vector machine classification Phylogeny bioinformatics Niobium Genomics Sequences Decision trees Training data

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Estimating recombination rate distribution by optimal quantization

Estimating recombination rate distribution by optimal quanti...

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ieee conference on bioinformatics

作者： M. Song S. Boissinot R.M. Haralick I.T. Phillips Department of Computer Science Queen's College Flushing NY USA Department of Biology Queen's College Flushing NY USA Doctoral Program in Computer Science Graduate CenterCity College and Graduate Center City University of New York New York NY USA

We obtain recombination rate distribution functions for all human chromosomes using an optimal quantization method. This nonparametric method allows us to control over-/under-fitting. The piece-wise constant recombination rate distribution functions are convenient to store and retrieve. Our experimental results showed more abrupt distribution functions than two recently published results. In the previous results, the over-/under-fitting issues were not addressed explicitly. Our estimation had greater log likelihood over a previous result using Parzen window. It suggests that the optimal quantization technique might be of great advantage for estimation of other genomic feature distributions.

关键词： Quantization Biological cells Distribution functions Humans Computer science Educational institutions bioinformatics Evolution (biology) Biology Genomics

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computational prediction of DtxR regulon - a dissection of physiological process controlled by DtxR in Corynebacterium species

Computational prediction of DtxR regulon - a dissection of p...

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ieee conference on bioinformatics

作者： S. Yellaboina P. Chakhaiyar S.E. Hasnain R. Ranjan Centre for DNA Fingerprinting and Diagnostics EMB India Node Hyderabad India

We developed a user friendly software tool to identify the potential binding sites of any regulatory protein based on Shannon relative entropy method. Known DtxR binding sites of Corynebacterium diphtheriae (C. diphtheriae) were used to generate a position specific reference profile for DtxR which was used to identify the potential DNA binding sites within the upstream sequences of Corynebacterium glutamicum (C. glutamicum) genes. In addition, DtxR regulated operons were also identified taking into account the predicted DtxR regulatory sites and Rho-independent transcription termination sites. The analysis predicted the binding sites upstream to a number of genes/operons which code for proteins involved in hemolysis and haemin transport. The analysis also predicts the binding sites upstream to genes that are involved in iron storage and oxidative stress defense including ferritin, starvation inducible DNA binding protein (Dps) and a homologue of endonuclease VIII (Nei). Both Dps and Nei homologue could be involved in controlling ferrous iron induced DNA damage.

关键词： Process control Entropy bioinformatics DNA Sequences Iron Genomics Frequency Software tools Proteins

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A block coding method that leads to significantly lower entropy values for the proteins and coding sections of Haemophilus influenzae

A block coding method that leads to significantly lower entr...

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ieee conference on bioinformatics

作者： G. Sampath Department of Computer Science College of New Jersey Ewing NJ USA

A simple statistical block code in combination with the LZW-based compression utilities gzip and compress has been found to increase by a significant amount the level of compression possible for the proteins encoded in Haemophilus influenzae, the first fully sequenced genome. The method yields an entropy value of 3.665 bits per symbol (bps), which is 0.657 bps below the maximum of 4.322 bps and an improvement of 0.452 bps over the best known to date of 4.118 bps using Matsumoto, Sadakane, and Imai's Iza-CTW algorithm. Calculations based on a compact inverse genetic code show that the genome has a maximum entropy of 1.757 bps for the coding regions, with a possibly lower actual entropy. These results hint at the existence of hitherto unexplored redundancies that do not show up in Markov models and are indicative of more internal structure than suspected in both the protein and the genome.

关键词： Block codes Entropy Proteins bioinformatics Biological information theory Genomics Distributed computing Biology computing Data mining Chemicals

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Identification of contaminants in proteomics mass spectrometry data

Identification of contaminants in proteomics mass spectromet...

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ieee conference on bioinformatics

作者： M. Duncan K. Fung H. Wang C. Yen K. Cios University of Colorado Health Sciences Center USA University of Colorado Denver USA

This paper discusses the identification of potential contaminants in mass spectrometry data derived from proteomic studies. Contaminant masses are usually submitted with valid peptide masses to the protein identification algorithms which can potentially lead to false positive results. In this paper we present an approach for the automatic identification of contaminant masses so that they can be removed prior to the submission of the peak list for protein identification. For this purpose we have developed an algorithm that clusters mass values. We calculate the frequencies of all masses and then identify possible contaminant masses. We propose that masses that occur with high frequency are contaminants. In our analysis of 78,384 masses derived from 3,029 proteins, we identify 16 possible contaminants. Of these 16, four are known trypsin autolysis peptides. Removing these contaminant masses from the database search will lead to more accurate and reliable protein identification.

关键词： Proteomics Mass spectroscopy bioinformatics

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cWINNOWER algorithm for finding fuzzy DNA motifs

cWINNOWER algorithm for finding fuzzy DNA motifs

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ieee conference on bioinformatics

作者： S. Liang NASA Advanced Spercomputing Division NASA Ames Research Center CA USA

The cWINNOWER algorithm detects fuzzy motifs in DNA sequences rich in protein-binding signals. A signal is defined as any short nucleotide pattern having up to d mutations differing from a motif of length l. The algorithm finds such motifs if multiple mutated copies of the motif (i.e., the signals) are present in the DNA sequence in sufficient abundance. The cWINNOWER algorithm substantially improves the sensitivity of the winnower method of Pevzner and Sze by imposing a consensus constraint, enabling it to detect much weaker signals. We studied the minimum number of detectable motifs q/sub c/ as a function of sequence length N for random sequences. We found that q/sub c/ increases linearly with N for a fast version of the algorithm based on counting three-member sub-cliques. Imposing consensus constraints reduces q/sub c/ by a factor of three in this case, which makes the algorithm dramatically more sensitive. Our most sensitive algorithm, which counts four-member sub-cliques, needs a minimum of only 13 signals to detect motifs in a sequence of length N=12000 for (l, d)=(15,4).

关键词： Fuzzy systems DNA computing bioinformatics

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Probe design for large-scale molecular biology applications

Probe design for large-scale molecular biology applications

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ieee conference on bioinformatics

作者： V. VanBuren T. Yoshikawa T. Hamatani M.S.H. Ko Laboratory of Genetics Developmental Genomics and Aging Section National Institute on Aging National Institutes of Health Baltimore MD USA

Large-scale molecular biology technologies such as DNA microarrays and large-scale in situ hybridization (ISH) are used to gain an appreciation of global attributes in biological tissues and cells. Although many of these efforts use cDNA probes, an approach that makes use of designed oligo probes should offer improved consistency at uniform hybridization conditions and improved specificity, as demonstrated by various oligo microarray platforms. We describe a new Web-based application that takes FASTA-formatted sequences as input, and returns both a list of the best choices for probes and a full report containing possible alternatives. Probe design for microarrays may use a scoring routine that optimizes probe intensity based upon an artificial neural network (ANN) trained to predict the average probe intensity from the physical properties of the probe and a screen for possible cross-reactivity. This new tool should provide a reliable way to construct probes that maximize signal intensity while minimizing cross-reactivity.

关键词： Probes Large-scale systems DNA Artificial neural networks Sequences Aging bioinformatics Cells (biology) Laboratories Genetics

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