The multiassembly problem: Reconstructing multiple transcript isoforms from EST fragment mixtures

Yi Xing

doi:10.1101/gr.1304504

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The multiassembly problem: Reconstructing multiple transcript isoforms from EST fragment mixtures

2004-02-12

邢

邢奕 (Yi Xing)

Alissa Resch

Christopher Seungkyu Lee

DOI：10.1101/gr.1304504

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Abstract

En 中文

Recent evidence of abundant transcript variation (e.g., alternative splicing, alternative initiation, alternative polyadenylation) in complex genomes indicates that cataloging the complete set of transcripts from ail organism is ail important project. One challenge is the fact that most high-throughput experimental methods for characterizing transcripts (Such as EST sequencing) give highly detailed information about short fragments of transcripts or protein products, instead of a complete characterization of a full-length form. We analyze this multiassembly problem-reconstructing the most likely set Of full-length isoform sequences from a mixture of EST fragment data-and present a graph-based algorithm for solving it. In a variety of tests, we demonstrate that this algorithm deals appropriately with coupling,a of distinct alternative splicing events, increasing fragmentation of the input data and different types of transcript variation (such as alternative splicing, initiation, polyadenylation, and intron retention). To test the method's performance oil pure fragment (EST) data, we removed all mRNA sequences, and found it produced no errors in 40 cases tested. Using this algorithim, we have constructed ail Alternatively Spliced Proteins database (ASP) from analysis Of human expressed and genomic sequences, consisting of 13,384 protein isoforms of 4422 genes, yielding an average of 3.0 protein isoforms per gene.

Keywords:

GLUCOCORTICOID MODULATORY ELEMENT

ALPHA MESSENGER-RNA

TIGR GENE INDEXES

FORK-HEAD FACTOR

RECEPTOR-ALPHA

MOLECULAR-CLONING

FACTOR-BINDING

PAIRED DOMAIN

EXPRESSION

PROTEIN