1. THE INSTITUTE FOR GENOMICS AND MULTISCALE BIOLOGY: CONFIDENTIAL
May 23, 2013
A Systems View of Alzheimer’s Disease
Icahn Institute: Stay connected with us!
@multiscalebio

2. Considering the digital universe of data to better diagnose and treat patients

3. Integrating data to build predictive models of living systems
( - DNA, - RNA, - Protein, - Metabolite)

4. Cell 153: 707-720 (2013)

5. PACIFIC BIOSCIENCES™ CONFIDENTIAL
Networks can be linked to human forms of disease to help
motivate relevance for human treatments
Isolate DNA and
genotype
Genotype
Isolate RNA and
sequence or profile
Atherosclerotic
Arterial wall
Atherosclerosis-
Free Artery Wall
(IMA)
Carotid and
coronary LesionLiver
Macrophages*
Blood monocytes
Omental and Mediastinal
Visceral Fat
Skeletal Muscle Subcutaneous
Fat
3 different parts
of brain
AND
Thousands of individuals now genotyped and profiled

6. PACIFIC BIOSCIENCES™ CONFIDENTIAL
Connections between diseases and tissues: IBD network
driving Alzheimer’s
Building networks from 500 prefrontal cortex samples

7. PACIFIC BIOSCIENCES™ CONFIDENTIAL
Constructing the co-expression networks
“Normal” versus LOAD Networks

8. Constructing predictive network models for AD

9. (Created with iCAVE from Gumus Lab, 2013)

10. (Created with iCAVE from Gumus Lab, 2013)

11. Causal probabilistic network relating to a PFC module correlating with multiple LOAD
clinical covariates, enriched for immune function/pathways related to microglia activity
Two papers in NEJM today
reporting on rare variants in
TREM2 associate with LOAD
We identified TYROBP
as a key regulator of
this network
CD33, MS4A4A,
MS4A6A
(from LOAD
GWAS)

12. The microglia pathogen phagocytosis pathway
TREM2 signals directly via TYROBP

14. Core disease modules harbor pluripotent drug targets

15. Acknowledgements
15
Mount Sinai PacBio Cornell CSHL
Ali Bashir
Bobby Sebra
Joel Dudley
Andrew Kasarskis
Milind Mahajan
Gintaras Deikus
Jun Zhu
Bin Zhang
Rui Chang
Michael Linderman
Gaurav Pandey
Bojan Losic
Omar Jabado
Glenn Farrell
Jason Chin
Yan Gao
Greg Khitrov
Frank Boellmann
Ellen Paxinos
David Rank
Paul Peluso
Edwin Hauw
Chris Mason
Roger Altman
Russell Durrett
Richard McCombie
Eric Antoniou
Patricia Mocombe
New York Genome
Center Sage Bionetworks University of Bonn Icelandic Heart
Association
Bob Darnell Stephen Friend
Chris Gaiteri
Harald Neumann
Liviu-Gabriel Bodea
Valur Emilsson
Stay connected with us!
@multiscalebio