1. Is the $1000 Genome as Near as We Think
Is the $1000 Genome as Near as We Think? A Cost Analysis of Next-Generation Sequencing
K.JM. van Nimwegen, R.A. van Soest, J. A. Veltman, M. R. Nelen, G. J. van der Wilt, L. ELM. Vissers, and J. PC. Grutters
November 2016
© Copyright 2016 by the American Association for Clinical Chemistry

2. Introduction
Technological advancements and simultaneously dropping costs of next-generation sequencing (NGS) have taken place in recent years
Commercial parties claim to be able to sequence an entire human genome for < $1,000
However, a complete and valid cost overview of NGS applications is currently lacking
Objective: to provide a complete, and up-to-date overview of the
real costs of three NGS applications: Targeted gene panels,
whole exome sequencing, and whole genome sequencing

3. Question 1
Why would breaking the $1,000 genome barrier be such a breakthrough? Which consequences would this have?

4. Methods (I)
Cost calculations were based on list prices, and the following assumptions:
TGP
WES
WGS
Platform
NextSeq 500
HiSeq4000
HiSeqX5
Life cycle (years) 5
Average coverage
100x
70x
30x
Utilization rate
10%
75%
Data storage (Gb/sample) 1
150
600
Data storage (years)
Table 1.
Base case assumptions. TGP = targeted gene panel; WES = whole exome sequencing; WGS = whole genome sequencing

5. Methods (II) Costs were divided into three categories:
Capital costs (non-recurring costs for equipment)
Maintenance costs
Operational costs (costs for running the sample)
All costs were calculated per sample

6. Methods (III)
Sensitivity analyses to anticipate future cost developments
From these, a best case and worst case scenario were constructed  Lower and upper bound of NGS costs
TGP
WES
WGS
Capital costs
- 50%
Consumable costs
Life cycle
3 – 5 years
Average coverage
30x – 100x
Utilization
1% - 15%
55% - 95%
Table 2.
Sensitivity analyses

7. Question 2
What can you say about the transferability of the results of this study between laboratories within and between countries? And how can you deal with cost components that aren’t directly transferable?

8. Results (I) Costs in euro’s TGP WES WGS Capital costs 1.89 35.19
175.33
Maintenance costs
0.91
12.29
72.04
Operational costs
330.10
744.27
1,421.64
Obtaining and extracting DNA
42.17
Sample preparation
242.62
296.68
27.61
Sequencing
4.56
262.24
1,057.81
Lab personnel
8.97
70.08
Data processing and storage
0.55
10.75
130.00
Data interpretation and report
31.23
62.65
93.97
Total per-sample costs
€333
€792
€1,669
Table 3.
Per-sample costs of TGP, WES, and WGS. TGP = targeted gene panel; WES = whole exome sequencing; WGS = whole genome sequencing

9. Results (II) Costs in euros TGP WES WGS Base case 333 792 1,669
Capital costs -50%
332
775
1,582
Consumable costs -50%
209
513
1,126
Life cycles of 3 years
334
810
1,761
30x coverage
328
615
100x coverage
929
5,430
Lower utilization (1%; 55%; 55%)
358
809
1,759
Higher utilization (15%; 95%; 95)
782
1,617
Table 4.
Sensitivity analyses

10. Results (III) Costs in euros TGP WES WGS Capital costs -50% Current
Consumable costs
Life cycle (years) 5 3
Utilization
15%
95% 1%
55%
Required coverage
30x
100x
Per-sample costs (€)
205
401
1,006
368
989
6,157
Table 5.
Best case and worst case scenario analyses

11. Question 3
What is needed to achieve the $1,000 genome in the future? How likely is it that this is going to happen, and why?

12. Discussion
This study included a complete, and up-to-date overview of the costs of diagnostic NGS applications
$1,000 genome not yet achieved
Only approached in very optimistic best case scenario
Per sample costs of WGS considerably higher than WES and
TGP. This does not imply that WGS should not be used in
clinical practice. Choice of NGS application depends also on its
effectiveness (diagnostic yield).
For each patient population, the choice of NGS applications and
sequencing depth should be based on a careful trade-off
between costs and consequences for the patient