My thoughts on sharing genotype and phenotype data

Today, Google and Broad Institute (my employer) have announced that they are teaming up to tackle genomic data. One sentence caught my attention: “Broad Institute has … either sequenced or genotyped the equivalent of more than 1.4 million biological samples”. Can we get the data?

Current data sharing model

In my limited experience, the current data sharing model is largely trust-and-distribute. Principle investigators (PIs) submit a form stating they will use controlled data properly. Upon approval, they can download (usually de-identified) individual genotypes and phenotypes and analyze locally.

In my view, this model has two issues. Firstly, it is insecure. The model puts all the trust on PIs and their PhDs/Postdocs/staffs. If one of them discloses confidential data, there is a breach. Secondly, it hampers data sharing. PIs may need to access multiple data sets. Getting approval for all of them is not trivial. In addition, many more researchers are not qualified to access data at all. For example, some sensitive data are not allowed to be transferred out of the border of a country.

Data access patterns

To address the issues, we need to first understand how we use genotype and phenotype data. It seems to me that we often, though not always, care about the aggregate of genotypes instead of indivial genotypes. We download genotype/phenotype data only to collect aggregate information with scripting. For example, we may ask which gene in cases have high loads of rare mutations or whether a particular SNP has high frequency in cases but low in controls or some statistics stratified by a phenotype (e.g. BMI or populations). Having aggregate data available is already very helpful.

A different data sharing model

So, here is my thought: a better data sharing model is to let users publicly query the aggregate statistics of their interest while hiding individual-level data and keeping samples unidentifiable. The server sees all the genotypes and phenotypes, processes the data and returns the aggregate to users.

How to make sure samples are unidentifiable is not easy. Here are a couple of ideas. We may disallow query of frequency data among a small number of samples. With one query, users would not know what sample has a particular allele. However, depending on the structure of phenotypes, there is a small chance that users may be able to infer the genotypes of a particular sample by performing multiple queries. A stronger idea is to cluster samples based on phenotypes and for each cluster, to use the median values to represent all samples in the cluster. Users will not get individual-level details beyond a cluster.

Implementing the new model

To make this new data sharing model something real, we need a highly flexible and performant genotype server that computes user-defined aggregate on the fly. It should at least match the expressiveness of SQL queries like:

SELECT v.chrom,v.pos FROM Variant v, Sample s, Genotype g
    WHERE v.gene="BRCA1" AND s.pop="CEU" AND g.vid=v.vid AND g.sid=s.sid
    GROUPED BY g.vid HAVING maf(g.gt)>0.01

The key requirement is to have users flexibly defining their own ways to slice and aggregate data. Precomputing a few summary statistics is a good start, but is inadequate for complex use cases.

Implementation is not enough

The idea of sharing aggregate data publicly will remain an idea unless authorities such as IRB approves to share data this way. It is very hard, near to impossible, but I do believe that this direction in general will make data sharing more open, efficient, convenient and secure.

A final comment

Many researchers are screaming for more samples, but in fact we already have probably a couple of million genotyped/sequenced samples world wide. These data are just locked up in attic. It is a pity. I have thoughts, but do not have practical solutions.