USING GPU AND POWER8 TO EXPLORE HOW GENOMES FOLD

Ido Machol

Aiden Lab Baylor College of Medicine

GTC 2015

THE IS LONG!

3 BILLION Letters 2 METERS …CGTTTACGAAAATCGCAAAACTTTCGATACCCATAGGCTACTGATCATACGACCGTTTACGAAAATCGAAACCTTTCCGATCTAGGCTAC…

Cell Nucleus

6 μm 100 Mb

10 Mb

1 Mb

100 Kb

10 Kb

1 Kb

100 bp

10 bp SAME GENOME, DIFFERENT FUNCTIONS PART I: TECHNOLOGY MICROSCOPY & FLUORESCENT IN SITU HYBRIDIZATION FISH CONTACT MAPPING Exploring structure via proximity

Times in the Same Photo

0-3 (lives far away)

4-11

FACEBOOK (lives nearby) CONTACT MAP

Always (same person)

Homer 2 0 1 2 1 0 1 0 0 4 5 6 7 8 9 10 11 12 13 14 0 3 2 1 0 0 0 0 0 1 2 16 6 5 4 11 1 1 2 0 1 2 1 0 1 0 0 Simpsons' 2 1 6 8 6 3 4 0 0 0 3 2 1 0 0 0 0 0 Contact 1 0 5 6 8 4 5 1 0 1 2 16 6 5 4 11 1 1 Map 0 0 4 3 4 5 5 0 0 2 1 6 8 6 3 4 0 0 # of Pictures 1 0 11 4 5 5 11 1 1 1 0 5 6 8 4 5 1 0 Together 0 0 1 0 1 0 1 2 1 0 0 4 3 4 5 5 0 0 0 16 0 0 1 0 0 0 1 1 1 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 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

Sequence

…CTGCCTCCTCGCGG CCGCGTGGTGGCAG…

Align to reference genome … … DNA Reference Alignment is not trivial

…CTGCC_TCCTCGCGG…

Insertion

Deletion

Substitution

…CTGAA_TCCTCGCGG……CTGC__TCCTCGCGG… …CTGCC CTCCTCGCGG… Computational HW and SW setup Rice RSCG PowerOmics hardware

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

GPUs

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) 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

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

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 …CTGCCTCCTCGCGG… About 27 hours Genome

Hi-C GENERATES GENOME- WIDE CONTACT MAPS Chromosome Genome

Hi-C GENERATES GENOME- WIDE CONTACT MAPS GenomeChromosome 8

Hi-C GENERATES GENOME- WIDE CONTACT MAPS

0 700

Reads/250 kb2 A

Hi-C GENERATES GENOME- A WIDE CONTACT MAPS

0 700

Reads/250 kb2 A B

Hi-C GENERATES GENOME- A WIDE CONTACT MAPS

B

0 700

Reads/250 kb2 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

PART II: BIOLOGY Genomic analysis of compartments

The two compartments correlate strongly with open and closed chromatin Genes Chromosome 14 1001 Mbkb2 Pixels 1 2 3 4 5 6 7 8

9 10 11 12 13 14 15 16

17 18 19 20 21 22 X

The whole genome is plaid A TOUR OF THE NUCLEUS

Organization observed at three distinct scales

NUCLEAR SCALE CHROMOSOME SCALE MEGABASE SCALE

100Mb 10Mb 1Mb

Organization observed at three distinct scales

NUCLEAR SCALE CHROMOSOME SCALE MEGABASE SCALE

100Mb 10Mb 1Mb

Organization observed at three distinct scales

NUCLEAR SCALE CHROMOSOME SCALE MEGABASE SCALE

100Mb 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, , Erez Lieberman Aiden

Cell 2014 30 million contacts More Contacts,HigherMore Resolution

5 billion contacts

Detection of Chromatin Loops Genome- wide via Hi-C

A+2ε B-2ε

A+ε B-ε

A B

ε B+2ε A-2 A-ε B+ε Into the loops

L1 L2 L3

L1 L2 L3 Computational Challenge III Loop calling

Which one shows a loop? 3D Map Features

X

✔

X

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

Lymphoblastoid cell Lung fibroblast 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 GREETINGS FROM Aiden Lab Broad Institute Erez Lieberman Aiden Eric Lander ANOTHER DIMENSION Suhas Rao Jim Robinson

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