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The Alternative Splicing Mutation Database: A hub for investigations of alternative splicing using mutational evidence

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BMC Research Notes 2008年第1期1卷 1-7页

作者： Bechtel, Jason M. Rajesh, Preeti Ilikchyan, Irina Deng, Ying Mishra, Pankaj K. Wang, Qi Wu, Xiaochun Afonin, Kirill A. Grose, William E. Wang, Ye Khuder, Sadik Fedorov, Alexei Program in Bioinformatics and Proteomics/Genomics University of Toledo Health Science Campus Toledo OH 43614 United States Dept. of Medical Microbiology and Immunology University of Toledo Health Science Campus Toledo OH 43614 United States Dept. of Basic Pharmaceutical Sciences South Carolina College of Pharmacy University of South Carolina Columbia SC 29208 United States Department of Biological Sciences Bowling Green State University Bowling Green OH 43403 United States College of Engineering University of Toledo Toledo OH 43606 United States Dept. of Medicine University of Toledo Health Science Campus Toledo OH 43614 United States

Background. Some mutations in the internal regions of exons occur within splicing enhancers and silencers, influencing the pattern of alternative splicing in the corresponding genes. To understand how these sequence changes affect splicing, we created a database of these mutations. Findings. The Alternative Splicing Mutation Database (ASMD) serves as a repository for all exonic mutations not associated with splicing junctions that measurably change the pattern of alternative splicing. In this initial published release (version 1.2), only human sequences are present, but the ASMD will grow to include other organisms, (see Availability and requirements section for the ASMD web address). This relational database allows users to investigate connections between mutations and features of the surrounding sequences, including flanking sequences, RNA secondary structures and strengths of splice junctions. Splicing effects of the mutations are quantified by the relative presence of alternative mRNA isoforms with and without a given mutation. This measure is further categorized by the accuracy of the experimental methods employed. The database currently contains 170 mutations in 66 exons, yet these numbers increase regularly. We developed an algorithm to derive a table of oligonucleotide Splicing Potential (SP) values from the ASMD dataset. We present the SP concept and tools in detail in our corresponding article. Conclusion. The current data set demonstrates that mutations affecting splicing are located throughout exons and might be enriched within local RNA secondary structures. Exons from the ASMD have below average splicing junction strength scores, but the difference is small and is judged not to be significant. © 2008 Bechtel et al;licensee BioMed Central Ltd.

关键词： Alternative Splice Splice Effect Splice Junction Alternative Splice Effect mRNA Isoforms

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Calculation of splicing potential from the alternative splicing mutation database

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BMC Research Notes 2008年第1期1卷 1-6页

Background. The Alternative Splicing Mutation Database (ASMD) presents a collection of all known mutations inside human exons which affect splicing enhancers and silencers and cause changes in the alternative splicing pattern of the corresponding genes. Findings. An algorithm was developed to derive a Splicing Potential (SP) table from the ASMD information. This table characterizes the influence of each oligonucleotide on the splicing effectiveness of the exon containing it. If the SP value for an oligonucleotide is positive, it promotes exon retention, while negative SP values mean the sequence favors exon skipping. The merit of the SP approach is the ability to separate splicing signals from a wide range of sequence motifs enriched in exonic sequences that are attributed to protein-coding properties and/or translation efficiency. Due to its direct derivation from observed splice site selection, SP has an advantage over other computational approaches for predicting alternative splicing. Conclusion. We show that a vast majority of known exonic splicing enhancers have highly positive cumulative SP values, while known splicing silencers have core motifs with strongly negative cumulative SP values. Our approach allows for computation of the cumulative SP value of any sequence segment and, thus, gives researchers the ability to measure the possible contribution of any sequence to the pattern of splicing. © 2008 Bechtel et al;licensee BioMed Central Ltd.

关键词： Splice Enhancer Exonic Splice Enhancer Code Potential Constitutive Exon 14th Exon

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Biologically Supervised Hierarchical Clustering Algorithms for Gene Expression Data

Biologically Supervised Hierarchical Clustering Algorithms f...

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Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)

作者： Grzegorz M Boratyn Susmita Datta Somnath Datta Kidney Disease Program and Clinical Proteomics Center University of Louisville Louisville KY Faculty of Depertment of Bioinformatics and Biostatistics University of Louisville Louisville KY

Cluster analysis has become a standard part of gene expression analysis. In this paper, we propose a novel semi-supervised approach that offers the same flexibility as that of a hierarchical clustering. Yet it utilizes, along with the experimental gene expression data, common biological information about different genes that is being complied at various public, Web accessible databases. We argue that such an approach is inherently superior than the standard unsupervised approach of grouping genes based on expression data alone. It is shown that our biologically supervised methods produce better clustering results than the corresponding unsupervised methods as judged by the distance from the model temporal profiles. R-codes of the clustering algorithm are available from the authors upon request

关键词： Clustering algorithms Gene expression Databases Algorithm design and analysis Biological system modeling Biology computing Cities and towns Data analysis Measurement standards Diseases

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Multiple alignment of continuous time series

Multiple alignment of continuous time series

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18th Annual Conference on Neural Information Processing Systems, NIPS 2004

作者： Listgarten, Jennifer Neal, Radford M. Roweis, Sam T. Emili, Andrew Department of Computer Science University of Toronto Toronto ON M5S 3G4 Canada Banting and Best Department of Medical Research Program in Proteomics and Bioinformatics University of Toronto Toronto ON M5S 3G4 Canada

ISBN: (纸本)0262195348

Multiple realizations of continuous-valued time series from a stochastic process often contain systematic variations in rate and amplitude. To leverage the information contained in such noisy replicate sets, we need to align them in an appropriate way (for example, to allow the data to be properly combined by adaptive averaging). We present the Continuous Profile Model (CPM), a generative model in which each observed time series is a non-uniformly subsampled version of a single latent trace, to which local rescaling and additive noise are applied. After unsupervised training, the learned trace represents a canonical, high resolution fusion of all the replicates. As well, an alignment in time and scale of each observation to this trace can be found by inference in the model. We apply CPM to successfully align speech signals from multiple speakers and sets of Liquid Chromatography-Mass Spectrometry proteomic data.

关键词： Time series

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Multiple alignment of continuous time series 04

Multiple alignment of continuous time series

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Proceedings of the 18th International Conference on Neural Information Processing Systems

作者： Jennifer Listgarten Radford M. Neal Sam T. Roweis Andrew Emili Department of Computer Science University of Toronto Toronto Ontario Banting and Best Department of Medical Research and Program in Proteomics and Bioinformatics University of Toronto Toronto Ontario

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In silico proteome analysis to facilitate proteomics experiments using mass spectrometry

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Proteome Science 2003年第1期1.0卷 1-15页

作者： Cagney, Gerard Amiri, Shiva Premawaradena, Thanuja Lindo, Michael Emili, Andrew Program in Proteomics/Bioinformatics Banting/Best Dept. of Medical Res. University of Toronto Toronto Ont. Canada Dept. of Molecular/Medical Genetics University of Toronto Toronto Ont. Canada Dept. of Clinical Pharmacology Royal College of Surgeons Dublin 2 123 Saint Stephen's Green Ireland

proteomics experiments typically involve protein or peptide separation steps coupled to the identification of many hundreds to thousands of peptides by mass spectrometry. Development of methodology and instrumentation in this field is proceeding rapidly, and effective software is needed to link the different stages of proteomic analysis. We have developed an application, proteogest, written in Perl that generates descriptive and statistical analyses of the biophysical properties of multiple (e.g. thousands) protein sequences submitted by the user, for instance protein sequences inferred from the complete genome sequence of a model organism. The application also carries out in silico proteolytic digestion of the submitted proteomes, or subsets thereof, and the distribution of biophysical properties of the resulting peptides is presented. proteogest is customizable, the user being able to select many options, for instance the cleavage pattern of the digestion treatment or the presence of modifications to specific amino acid residues. We show how proteogest can be used to compare the proteomes and digested proteome products of model organisms, to examine the added complexity generated by modification of residues, and to facilitate the design of proteomics experiments for optimal representation of component proteins. © 2003 Cagney et al;licensee BioMed Central Ltd.

关键词： bioinformatics Mass spectrometry Model organism Peptide Post-translational modification Proteome

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Conceptual design for an automated high-throughput magnetic protein complex purification workcell

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JALA - Journal of the Association for Laboratory Automation 2003年第6期8卷 101-106页

作者： Najmabadi, Peyman Goldenberg, Andrew A. Emili, Andrew Dept. of Mechanical/Industrial Eng. University of Toronto Toronto Ont. M5S3G8 5 King's College Road Canada Program in Proteomics/Bioinformatics Banting/Best Dept. of Medical Res. University of Toronto Toronto Ont. M5S 3G8 5 King's College Road Canada Robotics and Automation Laboratory Dept. of Mechanical/Industrial Eng. University of Toronto Toronto Ont. M5S 3G8 5 King's College Road Canada

One of the major challenges facing the emerging field of proteomics research is related to the technical difficulties in analyzing protein structure and function on a genomic scale. The routine purification of protein complexes as a means to investigate protein-protein interaction networks is of particularly high interest because of its significant potential to improve overall understanding of protein function and to improve ongoing drug discovery efforts. Automation of currently practiced laboratory procedures has the potential to markedly improve protein purification throughput, but important technical issues remain to be addressed. This paper investigates key bottlenecks in the automation of standard affinity-based procedures for protein complex purification and introduces a promising conceptual design for an automated workcell that would allow for rapid and efficient magnetic bead-based purification of protein complexes from model organisms suitable for a medium-sized research laboratory setting. The design specifications are based on a modular and flexible design that will permit routine, unattended batch isolation and processing of protein complexes from microbes.

关键词： Conceptual design Laboratory automation Laboratory robotics Magnetic purification Modular design Protein complex Protein purification proteomics

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A revised proof of the metric properties of optimally superimposed vector sets

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Acta Crystallographica Section A: Foundations of Crystallography 2002年第5期58卷 506-506页

作者： Steipe, Boris Department of Biochemistry Program in Proteomics/Bioinformatics University of Toronto Toronto Ont. Canada

A revised proof is given that the root-mean -square deviation between more than two vector sets after optimal superposition induces a metric. This corrects an error in a previous manuscript [Kaindl & Steipe (1997). Acta Cryst. A53, 809]. © 2002 International Union of Crystallography Printed in Great Britain - all rights reserved.

关键词： metric spaces root-mean-square deviation superposition.

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