U41 Grant Session

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Oct 23, 2013 (3 years and 9 months ago)

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www.iccg.org

U41 Grant Session

ISCA has
e
volved!

Established in 2007, ISCA was originally focused on

copy number array data.

Realizing our goals are not unique to
structural variation
, in
2012 we evolved into ICCG to include

sequence
-
level variation

efforts.

ICCG Membership


Over
190

member institutions


Over
2,400

individual members worldwide

2011

2012

2013

2009

2007

Timeline

Project Goals


To raise the quality of patient care by:


Standardizing

testing platforms and
data
interpretation
related to structural and sequence
-
level variation


Creating a
centralized

database

of clinically relevant
variant annotations to
share data

for clinical and
research purposes


Implementing a
QC

and
expert consensus process

for
curating data submitted across laboratories and
developing evidence based classifications



Bioinformatics and IT Workgroup

Joyce Mitchell (co
-
chair
)
and Sandy Aronson (co
-
chair
)

ARUP: David Crockett;
Cartagenia
: Steven Van
Vooren
; Emory:
Virenkumar

Patel;
GeneDx
: Rhonda Brandon;
Mayo: Eric Klee;
NCBI
: Deanna Church, Donna
Maglott
; George Riley; Partners Healthcare: Eugene Clark, Larry Babb, Siva
Gowrisanker
, Matt
Varugheese
, Tom
Venman
; University of Chicago
Teja

Nelakuditi
; Utah: Karen
Eilbeck

Sequence Variant Workgroup


Madhuri Hegde

(co
-
chair, Emory)

Sherri Bale (
co
-
chair, G
eneDx)

Soma Das (U Chicago)

Matt Ferber (Mayo)

Birgit Funke (Harvard/Partners)

Elaine Lyon (ARUP)

Heidi Rehm (Harvard/Partners)

Avni

Santani

(CHOP)

Patrick Willems (
Gendia
)


Structural Variant Workgroup


Erik
Thorland

(co
-
chair, Mayo)

Swaroop

Aradhya (co
-
chair, GeneDx)

Deanna Church (NCBI)

Hutton Kearney (Fullerton)

Charles Lee (Harvard/BWH)

Christa Martin (Emory)

Sarah South (ARUP)

Phenotyping Workgroup


David Miller (chair,
Harvard)

Ada
Hamosh

(Hopkins)

Mike Murray (Harvard/BWH)

Robert Nussbaum (USCF)

Erin Riggs (Emory)

Peter Robinson (Berlin)

Steven Van
Vooren

(Cartagenia)


Patrick
Willems

(
Gendia
)


Engagement, Education and
Access Workgroup


Andy
Faucett

(chair,
Geisinger
)

Erin Riggs (Emory)

Danielle
Metterville

(Partners)

Genetic Counselors from
participating laboratories


Consultants

Les Biesecker,
Johan
den
Dunnen
,
Robert Green,
Ada

Hamosh
, Laird Jackson, Stephen
Kingsmore
,

Jim
Ostell
,

Sue
Richards,
Peter
Robinson, Lisa Salberg, Joan Scott,
Sharon Terry

U41 Principal Investigators and Workgroups

NIH U41
PIs:

David Ledbetter (
Geisinger
), Christa Martin (
Geisinger
),

Joyce Mitchell (Utah), Robert Nussbaum (UCSF), Heidi
Rehm

(Harvard)

Structural Variant Workgroup

Co
-
Chairs:


Erik
Thorland

(Mayo) and
Swaroop

Aradhya

(
GeneDx
)


Goals:

1)
Use evidence
-
based review to assess genes/regions
targeted on ISCA array design

2)
Develop a genome
-
wide dosage sensitivity map

to
aid in clinical array interpretation and inform array
design


Haploinsufficiency

(loss) and/or
Triplosensitivity

(gain)


ISCA Participants

ARUP

Sarah South

Erica Andersen


Birmingham Women's NHS
Foundation

Dominic
McMullan


Emory University

Christa Martin

Erin
Kaminsky

Erin Riggs

Eli Williams

Vanessa
Horner


GeneDx

Swaroop

Aradhya

Daniel Pineda
-
Alvarez


Mayo Clinic

Erik
Thorland

Karen
Wain

Lindsey
Waltman



Mission
Health

Hutton Kearney


NCBI

Deanna Church


Victorian Clinical Genetics
Services

Damien Bruno




DDG2P

Matt
Hurles

Helen Firth

David
FitzPatrick


www.ncbi.nlm.nih.gov/projects/dbvar/ISCA

Sequence Variant Workgroup

Sequence Variant
Workgroup

Madhuri Hegde

(Co
-
Chair
, Emory)

Sherri Bale
(Co
-
Chair, GeneDx
)

Soma
Das (U Chicago)

Matt Ferber (Mayo)

Birgit
Funke

(Harvard/Partners)

Elaine
Lyon (ARUP
)

Heidi
Rehm

(Harvard/Partners
)

Avni

Santani

(CHOP)

Patrick Willems
(
Gendia
)

TBN from NCBI

TBN
from
CRVR

1.
Develop standards for variant
classification in conjunction with
ACMG, CAP, AMP


2.
Guide ClinVar Development


3.
Define the Medical
Exome


4.
Solicit and support labs to
submitting data


5.
Develop process for expert
consensus
-

8 pilot projects



Phenotyping Workgroup

David Miller (chair, Harvard/BCH
)

Ada
Hamosh

(Hopkins)

Mike Murray (Harvard/BWH)

Robert Nussbaum (USCF)

Erin Riggs (Emory
)

Peter Robinson (Germany)

Steven Van
Vooren

(Cartagenia)


Patrick
Willems

(
Gendia
)

Phenotyping Workgroup

1.
Develop approaches to
improve the collection of
phenotypic data for
association with
genotypes


2.
Ensure the use of
consistent and
compatible
terminologies and
ontologies across
interconnected
phenotype resources

Education, Engagement and
Access Working Group


Chair: Andy
Faucett

(
Geisinger
)


Members: Genetic counselors and ICCG project
managers


Educate stakeholders on ICCG efforts


Publications, webinars, booths at meetings, website


Engage groups to encourage submission of data


Labs, clinicians, researchers, patient advocacy
groups


Ensure access to data and resources is
appropriately managed

Bioinformatics and IT Workgroup

Co
-
Chairs: Joyce Mitchell and Sandy Aronson


ARUP/Utah:
David
Crockett, Karen
Eilbeck


Cartagenia
: Steven
Van
Vooren


Emory: Stuart
T
inker,
Viren

Patel

GeneDx
: Rhonda
Brandon

Mayo Clinic: Eric Klee

NCBI
:
Deanna
Church, Donna
Maglott
;

George Riley

Partners
Healthcare:
Eugene
Clark, Larry

Babb
,
Siva
Gowrisanker
, Matt
Varugheese
,

Tom
Venman


Univ

of Chicago:
Teja

Nelakuditi


1.
Facilitate communication between
laboratories, vendors and
NCBI


2.
Develop submission
standards
for
ClinVar


3.
Evaluate how labs are using
ClinVar and recommend
enhancements


4.
Support activities of other
workgroups



NCBI (ClinVar, dbSNP, dbVar, dbGaP, GTR) and EBI


Regulatory and Standards: ACMG, CAP, CDC, FDA, ASHG,
AMP, CMGS


NHGRI (CRVR, eMERGE, CSER, ROR)


IRDiRC


Locus Specific Databases (LSDBs


LOVD and non
-
LOVD)


InSiGHT
,
PharmGKB
,
MSeqDB
, CFTR2, ENIGMA,
etc


Human
Variome

Project, HGVS and LOVD


PhenoDB

(Ada Hamosh) and
Human Phenotype Ontology (Peter Robinson)


OMIM (Ada
Hamosh
) and
GeneReviews

(Bonnie
Pagon
)


Patient Advocacy Groups (Patient
CrossRoads
,
Genetic Alliance, UNIQUE
, Disease
Specific Groups)


Commercial Efforts



Working with Existing Efforts

Proposed U01/U41 Governance Structure

Note: pending funding decisions

Population

Genetics

Prenatal

GWAS

Non
-
coding

Standards/Data Collection Workgroups

Clinical
Domain Workgroups

Bioinformatics & IT Workgroups

Steering Committee

U41, UNC/
Geisinger
/ACMG,

Stanford/Baylor, NHGRI, NCBI

External
Stakeholder

Committee

Scientific Advisory
Board

UNC/
Geisinger
/ACMG
Executive Committee

Stanford/Baylor

Executive Committee

U41

Executive Committee

Phenotyping
WG

Medical
Exome

Cardio WG

Actionability

WG

Informatics WG

Curation

Tools WG

ClinVar

WG

Analysis

WG

JIRA CNV

EHR

WG

Cardio WG

Clinical Domain

WGs

PGx

PGx

WG

Sequence
Variant WG

Informatics WG

Bioinformatics and IT WG

Education, Engagement, Access WG

ELSI and Genetic Counseling WG

Data & Tool Dissemination WG

Epi genetics

Disease
Area
WGs

Structural

Variant WG

Sequence
Variant WG

Structural

Variant WG

Sequence
Variant WG

Structural

Variant WG

CoreDB

Disease Area Curation Tool

ClinVar/CRVR System Interactions

Note: pending funding decisions


OMIM

Patient

Registries

EHR Interface

Expert Curation of Genes and Variants by Clinical
Domain and Disease Area Workgroups

dbGaP

LSDBs

Labs

Labs

Labs

(Genotypes &

Phenotypes)

Gene

Resource

(Medical Exome,

Actionability)

CNV
Curation

Tool (JIRA)

Application
Interface

External Informatics

Activities Enabled

Expert

Curated

Variants

Case
-
level Data

Variant
-
level Data

ClinVar

Disease WGs

Clinical Domain WGs

Data

Crowd
-

sourced

Curation

Controlled Access

Public Access

Private

Pharm

GKB

Machine Learning
Algorithms

Population

Datasets

Medical

Lit

Portal for the Public

1.
Tell us you are interested

2.
Send us your data!


Send sample export of what you have

3.
Are you interested in curating?


Medical
exome

project


Disease area variant
curation

groups

4.
Help support the project by engaging with stakeholders


Opportunities to get involved