03
Jul

Replication and validation in -omics studies - just as important as reproducibility

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The psychology/social psychology community has made replication a huge focus over the last year. One reason is the recent, public blow-up over a famous study that did not replicate. There are also concerns about the experimental and conceptual design of these studies that go beyond simple lack of replication. In genomics, a similar scandal occurred due to what amounted to “data fudging”. Although, in the genomics case, much of the blame and focus has been on lack of reproducibility or data availability

I think one of the reasons that the field of genomics has focused more on reproducibility is that replication is already more consistently performed in genomics. There are two forms for this replication: validation and independent replication. Validation generally refers to a replication experiment performed by the same research lab or group - with a different technology or a different data set. On the other hand, independent replication of results is usually performed by an outside laboratory. 

Validation is by far the more common form of replication in genomics. In this article in Science, Ioannidis and Khoury point out that validation has different meaning depending on the subfield of genomics. In GWAS studies, it is now expected that every significant result will be validated in a second large cohort with genome-wide significance for the identified variants.

In gene expression/protein expression/systems biology analyses, there has been no similar definition of the “criteria for validation”. Generally the experiments are performed and if a few/a majority/most of the results are confirmed, the approach is considered validated. My colleagues and I just published a paper where we define a new statistical sampling approach for validating lists of features in genomics studies that is somewhat less ambiguous. But I think this is only a starting point. Just like in psychology, we need to focus not just on reproducibility, but also replicability of our results, and we need new statistical approaches for evaluating whether validation/replication have actually occurred.