What sequencing is used for

What do we do with sequencing?

Whole genome sequencing (WGS) reads an organism's entire genome. The first genome sequenced this way was that of the bacterium Haemophilus influenzae. The human genome project began in 1990 and was published in 2003; today a human genome can be read in days. The short reads are put together (assembled) by lining them up against a related reference genome, or, when there is none, from scratch (de novo assembly).

In medicine, WGS helps find the cause of inherited disorders, plan personalised treatment, and choose chemotherapy by looking at the variations in a patient's cancer cells.

Targeted sequencing reads only selected genes or regions, usually first copied by PCR, to find mutations, insertions and deletions. Clinical exome sequencing reads the known disease genes (listed in databases such as OMIM and HGMD), and is cheaper than WGS.

Sequencing can also answer specific questions:

• ChIP-Seq maps where a regulatory protein (such as a transcription factor) binds across the whole genome.
• RNA-Seq converts all the RNA in a cell into cDNA and sequences it, to measure the transcriptome: the number of reads for each gene shows how strongly it is expressed.

Metagenomics sequences the DNA of a whole community of microbes in a sample, without culturing them. Most microbes cannot be grown in the laboratory, so this reveals life we could not otherwise study: microbes of the gut or throat, of hot sulphur springs (a source of heat-stable enzymes), and viruses. Sorting out the mixed reads needs special computer algorithms.