New gene prediction method capitalizes on multiple genomes

Dec 20, 2007

Researchers at Stanford University report in the online open access journal, Genome Biology, a new approach to computationally predicting the locations and structures of protein-coding genes in a genome. Gene finding remains an important problem in biology as scientists are still far from fully mapping the set of human genes.

Furthermore, gene maps for other vertebrates, including important model organisms such as mouse, are much more incomplete than the human annotation. The new technique, known as CONTRAST (CONditionally TRAined Search for Transcripts), works by comparing a genome of interest to the genomes of several related species.

CONTRAST exploits the fact that the functional role protein-coding genes play a specific part within a cell and are therefore subjected to characteristic evolutionary pressures. For example, mutations that alter an important part of a protein's structure are likely to be deleterious and thus selected against. On the other hand, mutations that preserve a protein's amino acid sequence are normally well tolerated. Thus, protein-coding genes can be identified by searching a genome for regions that show evidence such patterns of selection. However, learning to recognize such patterns when more than two species are compared has proved difficult.

Previous systems for gene prediction were able to effectively make use of one additional 'informant' genome. For example, when searching for human genes, taking into account information from the mouse genome led to a substantial increase in accuracy. But, no system was able to leverage additional informant genomes to improve upon state-of-the-art performance using mouse alone, although it was expected that adding informants would make patterns of selection clearer.

CONTRAST solves this problem by learning to recognize the signature of protein-coding gene selection in a fundamentally different way from previous approaches. Instead of constructing a model of sequence evolution, CONTRAST directly 'learns' which features of a genomic alignment are most useful for recognizing genes. This approach leads to overall higher levels of accuracy and is able to extract useful information from several informant sequences.

In a test on the human genome, CONTRAST exactly predicted the full structure of 59% of the genes in the test set, compared with the previous best result of 36%. Its exact exon sensitivity of 93%, compared with a previous best of 84%, translates into many thousands of exons correctly predicted by CONTRAST but missed by previous methods. Importantly, CONTRAST's accuracy using a combination of eleven informant genomes was significantly higher than its accuracy using any single informant. The substantial advance in predictive accuracy represented by CONTRAST will further efforts to complete protein-coding gene maps for human and other organisms.

Further information about existing gene-prediction methods and the advance CONTRAST brings to the field can be found in a minireview by Paul Flicek, which accompanies the article by Batzoglou and colleagues.

Source: BioMed Central

Explore further: DNA tool helping biologists find elusive or invasive species

add to favorites email to friend print save as pdf

Related Stories

Boy or girl? Lemur scents have the answer

5 hours ago

Dozens of pregnancy myths claim to predict whether a mom-to-be is carrying a boy or a girl. Some say you can tell by the shape of a woman's bump, or whether she craves salty or sweet.

SOHO sees something new near the sun

7 hours ago

An unusual comet skimmed past the sun on Feb 18-21, 2015, as captured by the European Space Agency (ESA) and NASA's Solar and Heliospheric Observatory, or SOHO.

Train car design reduced impact in Southern California crash

7 hours ago

(AP)—After a horrific crash a decade ago that killed 11 people and injured 180 more, Southern California's commuter train network began investing heavily in passenger cars designed to protect passengers from the full force ...

Recommended for you

Chinese ivory traders find haven online

22 minutes ago

China's booming e-commerce websites have carried thousands of advertisements for illegal wildlife products including ivory, rhino horn and tiger bone, a wildlife trade monitoring network said on Tuesday.

Sizing up cells: Study finds possible regulator of growth

11 hours ago

Modern biology has attained deep knowledge of how cells work, but the mechanisms by which cellular structures assemble and grow to the right size largely remain a mystery. Now, Princeton University researchers ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.