View this webinar at: http://www.knome.com/webinar-ngs-informatics-and-interpretation-hardware-considerations. In this presentation, Knome’s Senior Vice President of Operations, Michael McManus, PhD, will review the k100 and k25 hardware models of the knoSYS including servers, storage, networks, and power components. While doing so, he will answer: - Why would someone purchase hardware when they can process NGS data on the cloud? - For an organization not interested in using the cloud, what sort of hardware should be considered? - What hardware specifications are needed for conducting align + call (FASTQ and/or BAM files) versus interpretation (VCF files)? - Is all hardware alike? How does someone compare systems apples-to-apples?

1. NGS Data Hardware Requirements
© 2014 Knome, Inc.!
and Considerations!
Presenter: Michael J. McManus, PhD, SVP of Operations!
Date: September 26, 2014!

2. © 2014 Knome, Inc.!
Questions!
If you have any questions during the
webinar, please enter them in the
GoToWebinar pane.
We will answer as many as possible
at the end.

3. © 2014 Knome, Inc.!
[Poll]!

4. ! ?
© 2014 Knome, Inc.!
During this webinar we will discuss
four questions:
"
1. Why purchase hardware when you can
process NGS data on the cloud?!
2. What sort of hardware should be
considered?!
3. What hardware specifications are
needed for conducting align + call
versus interpretation?!
4. How do I compare systems apples-to-apples?

5. Align!Call!Annotate!Filter!Classify!Report!
© 2014 Knome, Inc.!
NGS informatics and interpretation infrastructure!
Flexible, fast
bioinformatics
2
Comprehensive,
customizable
annotation
3
Indication-specific
filtering, prioritization, and
interpretation
Bioinformaticians &
Technologists
Geneticists, Clinicians, &
Genetic Counselors
1

6. © 2014 Knome, Inc.!
Why internal vs. using the cloud? !
§ Knome’s customers have
expressed a strong
preference for an internally
installed solution over a
cloud solution. Why? !
!
§ Three reasons:!
1. Security!
2. Software Version Control!
3. File Transfer Time!

7. ! ?
© 2014 Knome, Inc.!
During this webinar we will discuss
four questions:
"
1. Why purchase hardware when you can
process NGS data on the cloud?!
2. What sort of hardware should be
considered?!
3. What hardware specifications are
needed for conducting align + call
versus interpretation?!
4. How do I compare systems apples-to-apples?

8. © 2014 Knome, Inc.!
What type of hardware should be considered?!
§ To process NGS data you need to understand many
issues:!

9. © 2014 Knome, Inc.!
Elements for NGS informatics !
Five elements must be balanced:"
1. Compute!
• Multiple nodes!
• Grid Computing!
!
2. Database!
!
3. Storage!
• Shared File System!
4. Networks!
• Storage!
• Communications!
• File upload/download!
!
5. Software!
• Operating System!
• Virtualization!
• Open Source Tools!
• Web Server!

10. © 2014 Knome, Inc.!
knoSYS state diagram - node view!
Application node"
Grid node"
Database node"
File System Manager"
Data
nodes"

11. © 2014 Knome, Inc.!
Shared File System!
§ All files are stored in one place, not on separate nodes!
§ Failure tolerance is a requirement!
– RAID 6 protection is required !
– A minimum of 2 drive failures should be tolerated!
– One “hot spare” should be provided per array!
– Good array reliability rates (>90%)!
§ Performance is a key need!
– A file system that supports “striping” files across the storage array is
desired!
– A file system that gets faster as more disks are added to the storage array.!
– A minimum of a 1 Gigabyte per second of sustained I/O rate!

12. ! ?
© 2014 Knome, Inc.!
During this webinar we will discuss
four questions:
"
1. Why purchase hardware when you can
process NGS data on the cloud?!
2. What sort of hardware should be
considered?!
3. What hardware specifications are
needed for conducting align + call
versus interpretation?!
4. How do I compare systems apples-to-apples?

13. © 2014 Knome, Inc.!
What hardware is needed for align/call vs. interpretation? !
§ Aligning & Calling:"
– Aligning starts with a FASTQ, produces a BAM!
– Calling takes the BAM and produces a VCF!
– These processes require large amounts of RAM, disk
space, and CPU cores!
§ Interpretation:"
– Starts with a VCF file!
– The annotation and interpretation processes also benefit
from ample amounts of RAM, disk space, and CPU
cores, but can be done with far less. !

14. © 2014 Knome, Inc.!
The knoSYS® system overview!
§ End-to-end: reads to report!
§ Flexible, fast, secure!
§ Supports a multi-disciplinary
team!
§ Ideal for translational and
clinical labs!
§ Multiple configuration
options !
k100

15. © 2014 Knome, Inc.!
k100 model – for align/call, whole genomes!
§ The knoSYS k100 model will
efficiently process large numbers of
whole genomes and exomes. !

16. © 2014 Knome, Inc.!
k25 model – for interpretation!
§ The knoSYS k25 model is designed to efficiently process panels, as well
as smaller volumes of genomes and exomes.!

17. k100 Monthly Throughput"
" FASTQ" VCF-Only"
Sequence Type" Align/Call" Annotation"
Genomes (37x)! 60! 1,440!
Exomes (100x)! 270! 12,960!
Panels (300x )! 3,600! 64,800!
© 2014 Knome, Inc.!
Specs and Throughput!
k25 Specs"
Server"
#
Nodes"
CPU"
#
CPU"
#
Cores"
RAM
(GB)"
Storage
(TB)"
1 GbE +
card"
10GbE
card"
IB" UPS"
Compute" 1! E5-2640v2! 2! 16! 256! -! Yes! Yes! No!
No!
Database" -! -! -! -! -! -! -! -! -!
Storage" -! -! -! -! -! 24! -! -! -!
Total" 1" -" 2" 16" 256" 24" -" -" -" -"
k25 Monthly Throughput"
" FASTQ" VCF-Only"
Sequence Type" Align/Call" Annotation"
Genomes (37x)! 12! 360!
Exomes (100x)! 54! 3,240!
Panels (300x )! 720! 16,200!
k100 Specs"
Server"
#
Nodes"
CPU"
#
CPU"
#
Cores"
RAM
(GB)"
Storage
(TB)"
1 GbE +
switch"
10 GbE
card"
IB +
switch"
UPS"
Compute" 4! E5-2560v2! 8! 64! 512! 16!
Yes!
Yes!
Yes! Yes!
Database" 1! E5-2640v2! 2! 16! 128! 4! No!
Storage" 3! E5-2609! 3! 18! 48! 60! No!
Total" 8" -" 13" 98" 688" 80" -" -" -" -"

18. Storage" Parity"
© 2014 Knome, Inc.!
Lustre® Shared File System for the k100!
§ Two configurations:!
– 60TB and 180TB!
• 60 TB has 1 SSU!
• 180TB has 1 SSU and 2 ESUs!
§ Specs:!
– RAID 6 configuration!
– 20 x 4TB drives, plus 1 x 4TB hot spare !
for each SSU and each ESU!
– Max I/O !
• 60TB array ≈ 2.5 GB/sec!
• 180TB array ≈ 7.0 GB/sec!
• Matches Infiniband peak I/O rate of 7GB/sec!
– Array Reliability of 96.6%!
knoSYS k100 ClusterStor 1+0
TOTAL = 80TB / Usable = 60TB (4U)
SSU
0
OST
4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB
4TB
OST
4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB
knoSYS k100 ClusterStor 1+2
TOTAL = 240TB / Usable = 180TB (12U)
SSU
0
OST
4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB
4TB
OST
4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB
ESU
1
OST
4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB
4TB
OST
4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB
ESU
2
OST
4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB
4TB
OST
4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB

19. © 2014 Knome, Inc.!
RAID File System for the k25!
§ One configuration!
– 24TB usable / 32TB raw!
§ Specs:!
– RAID 6 configuration!
– 8 x 4TB drives!
• 6 x 4TB drives for storage!
– Max I/O !
• ≈ 900MB/sec!
– Array Reliability of 94.3%!
4TB 4TB 4TB 4TB 4TB 4TB 4TB 4TB
Storage" Parity"

20. ! ?
© 2014 Knome, Inc.!
During this webinar we will discuss
four questions:
"
1. Why purchase hardware when you can
process NGS data on the cloud?!
2. What sort of hardware should be
considered?!
3. What hardware specifications are
needed for conducting align + call
versus interpretation?!
4. How do I compare systems apples-to-apples?

21. © 2014 Knome, Inc.!
How do I compare systems apples-to-apples?!
§ All hardware sounds
similar, but the benefit of
the Knome solution is in:!
!
1. The unique combination
of the various hardware
elements!
!
2. The price-performance
that Knome provides for
its solution!
!
§ 5 Elements:!
!
– Compute!
– Database!
– Storage!
– Network!
– Software!

22. • Switch to manage and direct storage traffic"
• Switch to manage and direct network traffic"
• RDMS for managing storage of projects, sequences, etc.
PostgreSQL running on Lustre FS"
• Expanded Storage Unit (ESU) to add more capacity. Can
use 2TB, 3TB or 4TB drives. "
• Expanded Storage Unit (ESU) to add more capacity.
© 2014 Knome, Inc.!
knoSYS architecture – hardware!
QDR/FDR Infiniband Switch"
Gigabit Ethernet Switch"
Database Server"
ClusterStor Management Unit"
Scalable Storage unit"
30TB or 60TB usable"
Expanded Storage Unit 1"
30TB or 60TB usable"
Back-up Power Supply"
N
E
T
W
O
R
K
"
T
R
A
F
F
I"
C
S
T
O
R
A
G
E
"
T
R
A
F
F
I"
C
High Performance Computing Server"
Expanded Storage Unit 2"
30TB or 60TB usable"
• GRID NODES (3) to align, call, annotate, compare
genomes, exomes, and panels"
• APPLICATION NODE (1) for web-based GUI"
• ClusterStor Management Unit – Houses Metadata Server
(MDS) and Management Server (MGS)"
• Scalable Storage Unit (SSU) for a SHARED FILE SYSTEM
for storage of genomes, exomes, panels; projects,
analyses, etc."
Can use 2TB, 3TB or 4TB drives "
• BACK-UP POWER in case of power failure"
• CONDITIONS incoming power to prevent spikes/dips"

23. © 2014 Knome, Inc.!
knoSYS elements for NGS informatics - solution!
Component" Model k100" Model k25"
Compute and Database"
Compute nodes !
4 physical nodes, (3 compute nodes, !
1 application node)!
1 physical node with 3 virtual nodes !
(2 compute nodes, 1 application node)!
Grid Computing! Open Grid Engine / Open Grid Scheduler!
Database ! PostgreSQL node (physical)! PostgreSQL node (virtual)!
Storage"
Shared File System! Lustre! RAID 6 disk array!
Network
Storage Network! QDR/FDR Infiniband ! No network, uses SAS!
Communications
1Gb/s Ethernet for server-to-server communication!
Network!
10Gb/s Ethernet for file uploading and downloading!
Software"
Web Server! Tomcat (server-side), Java and Chrome (client-side)!
Operating System! CentOS 6.3 or higher!
Virtualization! N/A! VMWare vSphere ESXi!
Open Source Tools! Many open source tools!

24. © 2014 Knome, Inc.!
Conclusions!
§ The cloud has great potential, but for
today’s genomics needs, the focus is on an
in-house solution!
§ There is more to the decision than
hardware alone. You need to consider the
hardware and software when making your
decision!
§ There are many questions to be answered
before you can decide on your hardware
purchase!
§ Hardware is fairly similar, but there are
methods to combine hardware elements to
maximize performance, but at a reasonable
price. !
hardware
? k100

25. © 2014 Knome, Inc.!
What’s Next?!
§ A recording
of this
webinar and
the slides
will be
available on
our website
on Monday.!
www.knome.com
twitter.com/knome
info@knome.com
facebook.com/knomeinc
linkedin.com/company/knome-inc
617-715-1000

26. © 2014 Knome, Inc.!
Questions!
If you have any questions during the
webinar, please enter them in the
GoToWebinar pane.
We will answer as many as possible
at the end.