As I prepare to write my PhD dissertation, I have been reflecting on the state of genomics, particularly of publishing genomics. A question I sometimes get asked, which surprises me every time, is: “What is the point of sequencing the whole genome?” I admit, the first time I was shocked. But I tried to think about it from this other biologist’s perspective. From his point of view, sequencing a whole genome was all it really took to publish in a major journal. It is no simple task to sequence an entire genome, but it is more of a “data production” mode. Someone like him needs to go through ten or more individual, unique experiments to establish what a particular mutation in a particular gene is doing in a mouse before he can publish. I think biological scientists generally desire hypothesis-driven experimentation—answering a question by performing experiments. They see sequencing as just one big experiment. And maybe it is, but it also gives an incredibly large amount of information, making it a lot different from a single experiment of another type.
In our sequencing of the U87MG cell line, we tried to derive some biological relevance from the sequence and we did so by making general observations about the genome. For some biologists, this can in some ways feel lacking for some reason. For this reason, much of the field is moving toward whole exome sequencing in order to sequence the low-hanging fruit across a large number of samples rather than exploring the whole genome. They want to supplement their more traditional experimental approaches with next-gen sequencing, but they don’t see a point to whole genomes.
I think there’s a great deal of merit to that, but I also think there are important, biologically relevant questions that cannot be answered with whole exome alone, and therefore I do think there is need to perform whole genome studies in some cases. It all depends on the question being asked.