Transcriptomes are sometimes more useful than 'whole genomes'

The transcriptome is usually considered a lesser -ome and it’s often overlooked when we talk about rare disease diagnosis, but it shouldn’t be.

Transcriptomics is the study of the all of the RNA sequences that are present within a cell.

The transcriptome is a product of our genome and differences in RNA expression can regulate what proteins are ultimately made.

This determines the functions performed by our tissues which themselves are made up of trillions of cells, all with slightly different transcriptomes.

So for us to really, actually, understand anything about what our genome is doing at any given time, we need to look at the functional output of the genome.

This is especially important in the context of whole genome sequencing because it will find about 5 million variants, the vast majority of those having unknown effects.

And in some of the tougher to solve cases, where a deep intronic or non-coding variant results in disease, we can use transcriptome data to make sense of everything.

Transcriptomes give us 3 important read-outs:

A quantitative measure of gene expression - How much of each RNA is present? Anything missing? More than we expect?

The sequence of expressed transcripts - This is a bit like a double-check of genome sequencing. Do we find differences between what was in the DNA sequence and what is expressed in the RNA? Fusions?

Which isoforms are present - So the genome codes for like 22,000 genes but each of those genes can be alternatively spliced to create more than one version of a protein. 93% of genes undergo this process, so you can see how this can get complicated quickly. And if mutations affect splicing, we’ll see that in what bits of the genome actually make it into the RNA!

The biggest drawback of transcriptomes is that sometimes tissue specific collections are required, especially for muscular disorders, since the cells in our body don't all express the same RNAs.