Functional validation

Functional validation of genomic discoveries

To validate findings from high-throughput studies, which are discovery driven approaches, an assay that demonstrates how genetic differences can produce measurable phenotypic effects.

Functional validations are required to prove that the finding wasn't a consequence of chance alone, especially given widespread genetic variation in various samples.

Molecular assays

• Gene expression at the transcript level can be assayed using RNA-Seq or qRT-PCR.
• Tissue or intracellular localisation of transcripts and proteins
• Protein-DNA interaction using ChIP-Seq to identify sequences bound by specific proteins or histone modifications

Biological assays

• Use of cell lines to knockdown or transfect cells with a specific transcript and measuring a specific cellular phenotype
• Use of animal models to knock-out or knock-in transcripts

See http://massgenomics.org/2013/07/functional-validation-genomic-discoveries.html

On the definition of function

• http://sandwalk.blogspot.jp/2014/06/the-function-wars-part-i.html
• http://sandwalk.blogspot.jp/2014/07/the-function-wars-part-ii.html
• http://sandwalk.blogspot.jp/2014/07/the-function-wars-part-iii.html
• http://sandwalk.blogspot.jp/2014/08/the-function-wars-part-iv.html
• http://www.pnas.org/content/111/33/E3365.short
• http://www.jstor.org/discover/10.1086/676588

What fraction of the human genome is functional?

What fraction of the human genome is functional? - http://genome.cshlp.org/content/early/2011/08/26/gr.116814.110

The extent of functionality in the human genome - http://www.biomedcentral.com/content/pdf/1877-6566-7-2.pdf