Free Program Predicts How Troublesome a Genetic Mutation Is

smoothjazz writes "Researchers describe a new, freely available Web-based program called Spliceman for predicting whether genetic mutations are likely to disrupt the splicing of messenger RNA, potentially leading to disease. From the article: 'Spliceman makes its predictions about mutations by calculating that distance. It has successfully predicted the known effect of many mutations. The software has genomic information about 11 species: humans, chimpanzees, rhesus monkeys, mice, rats, dogs, cats, chickens, guinea pigs, frogs, and zebra fish.'"

Comments

Ruined by stupid PR

[pesho]

Free Program Predicts How Troublesome a Genetic Mutation Is

No it doesn't.

This is yet another case of how stupid PR does damage to otherwise good science. The original paper (not the PR release) describes a statistical model. The model tells you how likely it is for a mutation to affect splicing. According to ROC curve on figure 4 it isn't nearly as selective or sensitive as you need it to be for any clinical application. It is however a great research tool. The PR article makes another false assumption, by stating that mutations affecting the splicing of an exon invariably cause 'trouble'. In fact it is well established that there is a significant variability in exon usage in perfectly healthy humans (citations below).

1. Kwan, Tony, David Benovoy, Christel Dias, Scott Gurd, David Serre, Harry Zuzan, Tyson A. Clark, et al. “Heritability of Alternative Splicing in the Human Genome.” Genome Res. 17, no. 8 (August 1, 2007): 1210–1218.
2. Zhang, Wei, Shiwei Duan, Emily O. Kistner, Wasim K. Bleibel, R. Stephanie Huang, Tyson A. Clark, Tina X. Chen, et al. “Evaluation of Genetic Variation Contributing to Differences in Gene Expression Between Populations.” The American Journal of Human Genetics 82, no. 3 (March 3, 2008): 631–640.

Interesting, But Not The First

[Anonymous Coward]

This is an interesting program, but it's hardly the first (coming from a grad student in Bioinformatics studying variation in the cancer genome). There are a large number of programs attempting to determine the impact of variation in the genome. We use these in our work with the exome (enrichment and sequencing of just the known coding elements in the human genome). A much larger challenge is finding true positive base and indel variation from next-generation sequencing, where alignment and sequencing artifacts lead to many false positive signals.

Here are two of the most popular:
SiFT: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC168916/
PolyPhen: http://www.ncbi.nlm.nih.gov/pubmed/12202775?dopt=Abstract

-Lee

Re:Inbreeding

[Samantha Wright]

What sex education class in Arkansas?