This document describes a project at Novartis to use Apache Spark for high-dimensional data analysis from drug screening. Large datasets from various screening technologies were analyzed using Spark pipelines for quality control, normalization, and classification. Visualizations were built using WebGL. The goals were to speed up multi-day batch jobs, create a unified analysis workflow, and build an application for scientists. Future work includes elastic infrastructure, supervised learning of cell phenotypes, and contributing methods to open source.

1. Escaping Flatland: interactive
high-dimensional data analysis in
drug discovery using Spark
Josh Snyder, Victor Hong, Laurent Galafassi
Novartis Institutes for BioMedical Research (NIBR)

2. Overview
• Use case
– High-dimensional screening data
• Goals
– Production data pipelines for scientists
– Reusable analysis platform for informaticians
• High level architecture
– Spark and other components
• Outcome
– Achievements & impact
– Future work

3. Screening is scale-out for bench science
1
2
3
4

4. Data size depends on readout technology,
structure is standard
• Microscopy
• Cell morphometrics
• Image texture
• ...
• Sequencing
• Multiple gene expression
• Cytometry
• Multiple protein expression
5
6

5. Datasets can be large
1000 plates 1536 wells/plate 1k to 5k cells/well
50 to 2000 features/cell
1 to 10 billion observations
10 to 2000 features
10b to 20 trillion data points
10 GB to 20 TB
+ time points (x10 = 200TB)
+ ??
1 screen

6. Many features can be used to quantify activity
Active
Control
Neutral
Control
Nucleus/Cytoplasm Intensity
Cell Texture Variance (3 pixel)
…
n = 1000’s

7. We can only see what we look at
Cell Texture
Variance (3 pixel)
Nucleus/Cytoplasm
Intensity
Average Z’: 0.65Average Z’: 0.78
7

8. So we need to look at everything
Input
• All observations, all
features
QC
• Mask problem
observations
• Mask problem
features
• Calculate aggregate
measures for review
• Per feature
• Per observation
group
Normalization
• Pattern correction
and scoring for each
feature
• Eliminate
uninformative
features
Classification
• Use full feature
vectors to find cases
showing desired
activity/phenotype

9. Smells like Spark…
Data Pipeline
• Rows =
observations
• Columns =
features
Data Pipeline
• Column-wise
filtering and
aggregation
Data Pipeline
• Column-wise
correction and
scoring
• Column to column
correlation over
rows
Data Pipeline
• Row-wise
aggregation over
features to
compute distance
metrics

10. Spark is not a tool for bench scientists
Data Pipeline Data Pipeline Data Pipeline Data Pipeline
Visualization &
Control
Visualization &
Control
Visualization &
Control
Visualization &
Control
Algorithms
Workflow

11. High-dimensional data-driven architecture
• Pipelines for large data à
Spark
– Distribute computation
– Minimize IO for intermediate
results
– Declarative API
– Support for popular data analysis
languages
– Ecosystem: MLlib, Spark Job
Server, etc.
• Visualization & control à
WebGL
– Web UI flexibility
– Render millions of data points
• Query à Cassandra
– Spark Connector
– Distributed, fast, mature, key-value
/ column family store

12. Simple workflow

13. Rich, interactive visualizations

14. Methods implementations
• Classification
– Mahalanobis Distance
– Gaussian Naïve Bayes
• Coarse-grained utilities
– findNearLinearCombos
– findCorrelation
• Fine-grained utilities
– Streaming models for incrementally integrating data (pairwise
correlation, Greenwald-Khanna quantile estimations, et al.)
– Robust statistical measures (MAD, IQR, et al.)
– Data masking, missing values handlers (casewise, pairwise, imputation)

15. The big picture
• Achievements
– Multi-day batch jobs à multi-hour jobs
– Unified data format & workflow across readout technologies
– End user application for bench scientists
• Future work
– Elastic infrastructure
– Supervised learning of cell phenotypes
– Methods APIs for informaticians
– Contributions back to open source

16. The really big picture
Discovery of therapeutics
for patients in need
Informatics applications
Distributed complex
analytics
Spark

17. Acknowledgments
Nabil Hachem
Fred Harbinski
Ioannis Moutsatsos
Hanspeter Gubler
Sergey Kokorin
Leonid Volobuev
Marat Gazimullin
Evgeniya Condrashina
Alexey Girin
David Wilson
and the entire NIBR project team, stakeholders, & sponsors

18. Attributions
1. "1905 Otto Folin in biochemistry lab at McLean HospitalbyAHFolsom Harvard" by A H Folsom -
http://preserve.harvard.edu/photographs/McLean.html. Licensed under Public Domain via Commons -
https://commons.wikimedia.org/wiki/File:1905_Otto_Folin_in_biochemistry_lab_at_McLean_Hospital_byAHFolsom_Harvard.png#/media/Fil
e:1905_Otto_Folin_in_biochemistry_lab_at_McLean_Hospital_byAHFolsom_Harvard.png
2. "Petri dish at the Pacific Northwest NationalLaboratory" by Pacific Northwest NationalLaboratory, US Department of Energy -
http://picturethis.pnl.gov/picturet.nsf/by+id/DRAE-8DBTWP. Licensed under Public Domain via Commons -
https://commons.wikimedia.org/wiki/File:Petri_dish_at_the_Pacific_Northwest_National_Laboratory.jpg#/media/File:Petri_dish_at_the_Pacifi
c_Northwest_National_Laboratory.jpg
3. "ChemicalGenomics Robot" by Maggie Bartlett, National Human Genome Research Institute -
http://www.genome.gov/dmd/img.cfm?node=Photos/Technology/Research%20laboratory&id=79299. Licensed under Public Domain via
Commons - https://commons.wikimedia.org/wiki/File:Chemical_Genomics_Robot.jpg#/media/File:Chemical_Genomics_Robot.jpg
4. "385 multiwell plate 1" by real name: Nadina Wiórkiewiczpl.wiki: Nadine90commons: Nadine90 - Own work(dziękiwspółpracy ze szkołą
fotograficzną - Fotoedukacja /in cooperation with the schoolof photography - Fotoedukacja). Licensed under CC BY-SA 3.0 via Wikimedia
Commons - https://commons.wikimedia.org/wiki/File:385_multiwell_plate_1.jpg#/media/File:385_multiwell_plate_1.jpg
5. "Automated confocalimage reader" by Neil Emans IPK - self-made. Original image cropped in this usage. Licensed under CC BY-SA 3.0
via Wikipedia - https://en.wikipedia.org/wiki/File:Automated_confocal_image_reader.jpg#/media/File:Automated_confocal_image_reader.jpg
6. By Kierano - Own work. Original image cropped and resized in this usage. CC BY-SA 3.0,
https://commons.wikimedia.org/w/index.php?curid=25180061
7. "Flatland sphere". Licensed under Public Domain via Wikimedia Commons -
https://commons.wikimedia.org/wiki/File:Flatland_sphere.JPEG#/media/File:Flatland_sphere.JPEG

19. THANK YOU.
josh.snyder@novartis.com Presentation and project
victor.hong@novartis.com
laurent.galafassi@novartis.com
nabil.hachem@novartis.com NIBR Data Engineering