USING GPU AND POWER8 TO EXPLORE HOW GENOMES FOLD Ido Machol Aiden - - PowerPoint PPT Presentation

USING GPU AND POWER8 TO EXPLORE HOW GENOMES FOLD

Ido Machol Aiden Lab Baylor College of Medicine Rice University GTC 2015

THE HUMAN GENOME IS LONG!

…CGTTTACGAAAATCGCAAAACTTTCGATACCCATAGGCTACTGATCATACGACCGTTTACGAAAATCGAAACCTTTCCGATCTAGGCTAC…

3 BILLION Letters 2 METERS

Nucleus

Cell

6 μm

10 bp 100 bp 1 Kb 10 Kb 100 Kb 1 Mb 10 Mb 100 Mb

SAME GENOME, DIFFERENT FUNCTIONS

PART I: TECHNOLOGY

MICROSCOPY & FLUORESCENT IN SITU HYBRIDIZATION

FISH

CONTACT MAPPING

Exploring structure via proximity

4-11

(lives nearby)

0-3

(lives far away)

Always

(same person) Times in the Same Photo

FACEBOOK

CONTACT MAP

Homer

Simpsons' Contact Map

# of Pictures Together

2 0 1 2 1 0 1 0 0 0 3 2 1 0 0 0 0 0 1 2 16 6 5 4 11 1 1 2 1 6 8 6 3 4 0 0 1 0 5 6 8 4 5 1 0 0 0 4 3 4 5 5 0 0 1 0 11 4 5 5 11 1 1 0 0 1 0 1 0 1 2 1 0 0 1 0 0 0 1 1 1

16

Hi-C

3D Genome Sequencing

Hi-C: genome-wide Chromosome Conformation Capture

Erez Lieberman-Aiden, Nynke van Berkum et al. Science 2009

Computational Challenge I Alignment, calculate contacts

…CTGCCTCCTCGCGG CCGCGTGGTGGCAG…

DNA Reference Sequence Align to reference genome

… …

Alignment is not trivial

…CTGCC_TCCTCGCGG… …CTGC__TCCTCGCGG… …CTGAA_TCCTCGCGG… …CTGCCCTCCTCGCGG…

Substitution Deletion Insertion

Computational HW and SW setup

8 x Power8 Servers 2 Sockets x 12 cores x 8 threads = 192 virtual cores each Total of 1,536 virtual cores in cluster.

• 4 X 256GB RAM
• 2 X 1024GB RAM
• 2 X 256GB RAM

with NVIDIA K40 Tesla

Model 8247-22L and 8247-42L Byte order: BI-Endian

Rice RSCG PowerOmics hardware

Tesla K40

Stream Processors 2880 Core Clock 745MHz Boost Clock(s) 810MHz, 875MHz Memory Clock 6GHz GDDR5 VRAM 12GB Single Precision 4.29 TFLOPS Double Precision 1.43 TFLOPS (1/3)

GPUs

Storage

• IBM GPFS Storage Server (Model 24)
• 4 X JBOD
• Total of 361 TB fast scratch disk space
• (Up to 1.4 Peta bytes)
• FlashSystem 840 20TB Flash

Interconnect:

• 56 Gigabit 36-port FDR IB switch
• Mellanox Next gen Connect-IB FDR Host Channel Adapters
• 10-Gigabit Ethernet
• Internet 2

Interconnect

Rice RSCG PowerOmics software

Cluster management

• IBM Platform LSF, PPM, PAC, PowerKVM 2.1.0

Operating system

• Ubuntu 14.4 (little-endian) + Red Hat Enterprise Linux 7.0

Storage

• Mellanox OFED 2.4-1
• GPFS 4.1

Scientific

• BioBuilds 2014.11

Challenge -

Alignment of billions of contacts High Resolution Map

13 billion reads forming 5 billion contacts in the map

IBM Power8 Cluster

675 read alignments / second / CPU core 192 cores

About 27 hours

…CTGCCTCCTCGCGG…

Chromosome

Hi-C

GENERATES GENOME- WIDE CONTACT MAPS

Genome

Genome

Hi-C

GENERATES GENOME- WIDE CONTACT MAPS

Genome Chromosome 8

Hi-C

GENERATES GENOME- WIDE CONTACT MAPS

700 Reads/250 kb2

A A

Hi-C

GENERATES GENOME- WIDE CONTACT MAPS

700 Reads/250 kb2

A B A B

Hi-C

GENERATES GENOME- WIDE CONTACT MAPS

700 Reads/250 kb2

PART II: BIOLOGY

Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome

Erez Lieberman-Aiden, Nynke van Berkum et al. Science 2009 Science, 2009

Genomic analysis of compartments

Genes

Chromosome 14 Mb

2 Pixels

1

The two compartments correlate strongly with

• pen and closed

chromatin

kb

2 Pixels

100

The whole genome is plaid

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 X

A TOUR OF THE NUCLEUS

Organization

• bserved at three distinct scales

NUCLEAR SCALE 100Mb CHROMOSOME SCALE MEGABASE SCALE 10Mb 1Mb

Organization

• bserved at three distinct scales

NUCLEAR SCALE 100Mb CHROMOSOME SCALE MEGABASE SCALE 10Mb 1Mb

Organization

• bserved at three distinct scales

NUCLEAR SCALE 100Mb CHROMOSOME SCALE MEGABASE SCALE 10Mb 1Mb

A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping

Suhas Rao*, Miriam Huntley*, Neva Durand, Elena Stamenova, Ivan Bochkov, James Robinson, Adrian Sanborn, Ido Machol, Arina Omer, Eric Lander, Erez Lieberman Aiden Cell 2014

5 billion contacts 30 million contacts

More Contacts, Higher Resolution

Detection of Chromatin Loops Genome- wide via Hi-C

A A-2ε A-ε A+ε A+2ε B-ε B-2ε B B+ε B+2ε

Into the loops

L3 L2 L1 L1 L2 L3

Computational Challenge III

Loop calling

Which one shows a loop?

X ✔

X

3D Map Features

X

Computational Challenge III

Loop calling

• Apply 4 filters for each pixel.
• 20 Giga pixel image.
• Millions of parallel filters.

NVIDIA Tesla GPU

200x faster than previous CPU implementation – from 3 weeks to 3 hours.

10,000 Loops in the Human Genome

Loops turn genes on and off

Lung fibroblast cell Lymphoblastoid cell

SUMMARY OF COMPUTATIONAL EFFORTS

Sequence alignment proportions

Genome data production and analysis

• In about 36 months we produced sequence equivalent of more than

2200x coverage of the human genome.

• For reference, the Human Genome Project produced 12.6x coverage, over

the span of 4 years. Storage

• We currently have 25 TB of RAW sequenced data
• We sequence 1 TB each month.
• After processing the raw sequenced data, we store 3 TB of Raw and

processed data.

Computational speed up

Cluster processing

• We produce 1 Billion reads per month.
• Power8 is capable of processing alignments at 675 reads/second per CPU

core.

• 50% faster then the cluster system we were using before.
• At this speed, we consume about 17 “CPU days” per month.
• With power8 cluster having over 192 cores, the jobs complete processing

in about 2 hours. GPU processing

• Using NVIDIA Tesla K40, we run our loop calling algorithm over a 20Giga

pixel map 200x faster than CPU implementation.

• Instead of 3 weeks we get the work done in only 3 hours.

aidenlab.org/juicebox

Aiden Lab

Erez Lieberman Aiden

Suhas Rao Miriam Huntley

Neva C Durand Elena Stamenova Adrian Sanborn Arina Omer Ivan Bochkov Olga Dudchenko Robert Nnake Su-Chen Huang Muhammad Shamim Chris Lui Sarah Nyquist Sanjit Batra Ashok Cutkosky Najeeb Tarazi Jian Li Broad Institute Eric Lander Jim Robinson

GREETINGS FROM ANOTHER DIMENSION