Just 10 years ago it cost about $1,000 to sequence a million base pairs; today, it costs less than $0.10. Such a rapid decline in the expense of next-generation sequencing (NGS) has brought the technology out of the investigational realm into the daily clinical setting. In fact, several commercial entities claim they have broken the $1,000 barrier for sequencing an entire human genome.
However, the first study to objectively evaluate the actual costs of NGS revealed that the field is not quite there yet. The study, published in the November issue of Clinical Chemistry, reports the cost-effectiveness of three NGS applications: targeted gene panels (TGP), whole exome sequencing (WES), and whole genome sequencing (WGS) on the Illumina NextSeq500, HiSeq4000, and HiSeqX5 platforms, respectively.
In considering the total costs, Dutch researchers went beyond the cost of the sequencing itself and included spending on acquiring and maintaining equipment; the personnel needed for sample preparation, data interpretation, and reports; and the management and storage of large amounts of data. They divided costs into capital, maintenance, and operational categories.
The researchers found annual capital costs for WGS ($1.4 million) that were 6 and 27 times higher than capital costs for WES ($224,085) and TGP ($51,244), respectively, with per-sample capital costs of $190 for WGS, $38 for WES, and $2 for TGP.
Per-sample maintenance costs of WGS were $78, which is 6 and 79 times higher than for WES ($13) and TGP ($1), respectively.
Operational costs accounted for the largest part of the per-sample costs of NGS applications: $359 for TGP, $809 for WES, and $1,547 for WGS. Major cost drivers were the consumables required for sample preparation and sequencing.
Overall, the group estimated total per-sample costs of $362, $862, and $1,816 for TGP, WES, and WGS, respectively, meaning the hoped-for $1,000 genome remains out of reach.
However, when the researchers conducted a best-case sensitivity scenario of anticipated future cost developments, the per-sample cost of WGS approached $1,100.
This best-case scenario required very efficient and long-term application of the sequencing equipment, they wrote, as well as cost reductions of 50% in both capital and consumable costs, and technological advances allowing for 30X coverage.
On the other hand, short-term and inefficient use of the sequencing equipment, in combination with a sequencing depth of 100X, might increase the per-sample costs by 10.5%,
24.9%, and 268.9% for TGP, WES, and WGS, respectively.
The researchers were optimistic that it will not be long, however, before competition and economies of scale make the sub-$1,000 genome a reality.