National Center for Biotechnology Information - Genetic Alliance

110101

NCBI

National Center for Biotechnology
Information

•
Created by Public Law 100
-
607 in 1988 as part of
National Library of Medicine at NIH to:

•
Create automated systems for knowledge about molecular biology,
biochemistry, and genetics.

•
Perform research into advanced methods of analyzing and
interpreting molecular biology data.

•
Enable biotechnology researchers and medical care personnel to
use the systems and methods developed.

•
Builders and providers of GenBank, Entrez, Blast,
PubMed. Online systems host about 1.8 million users per
day at peak rates of 3,200 web hits a second.

•
Center for basic research and training in computational
biology.

110101

NCBI

NCBI is the most heavily site in
biomedicine. Why?

300,000

200,000

100,000

NCBI Web Traffic
–

1997
-
2006

400,000

January 1998

500,000

600,000

700,000

January 1999

January 2000

January 2001

January 2002

January 2003

January 2004

January 2005

January 2006

722,000 Unique IPs a Day

91 Million Web Hits a Day

3200 Peak Web Hits a Second

1.5 Terabytes FTP a Day

1.8 Million Unique Users a Day

110101

NCBI

Data, the Next Intel Inside

110101

NCBI

Comparative Analysis of Genes
Enables “Innovation in Assembly”

Human 638
RH
ACV
E
VQDEIA
FI
P
N
DVYFEKDKQMFH
IITGPNMGGKSTY
I
RQ
TGV
I
V
LMA
Q
IG
CF
VP
C

697

Yeast 657
RH
PVL
E
MQDDIS
FI
S
N
DVTLESGKGDFL
IITGPNMGGKSTY
I
RQ
VGV
I
S
LMA
Q
IG
CF
VP
C

716

E.coli 584
RH
PVV
E
QVLNEP
FI
A
N
PLNLSPQRR
-
ML
IITGPNMGGKSTY
M
RQ
TAL
I
A
LMA
Y
IG
SY
VP
A

642

Colon cancer gene sequence

3000 Myr

1000 Myr

500 Myr

Human

Fly

Worm

Yeast

Bacteria

Mouse

110101

NCBI

Entrez
: Pathway to Discovery

Amino acid
sequence similarity

Coding region
features

Nucleotide
sequence
similarity

Term frequency
statistics

Literature
citations in
sequence
databases

Literature
citations in
sequence
databases

MEDLINE
abstracts

Nucleotide
sequences

Protein
sequences

110101

NCBI

Entrez Increases Discovery Space

Nucleotide
sequences

Protein
sequences

Taxon

Phylogeny

3
-
D
Structure

MMDB

3
-
D
Structure

PubMed
abstracts

Complete
Genomes

PubMed

Entrez
Genomes

Publishers

Genome
Centers

110101

NCBI

Elements of WGA


Phenotype Model


Genotype


Association between Phenotype Model and
Genotype

110101

NCBI

Elements of Phenotype


Protocols, Questionnaires, Documentation

•
Best explanation of measured attributes

•
Basically Text, often on paper or scanned PDF

•
Often unavailable even to sponsoring IC



Data



Data Dictionary




110101

NCBI

Elements of Phenotype


Protocols, Questionnaires, Documentation



Data

•
Measured attributes in a square table

•
Row is individual

•
Column is measure

•
Column names often obscure (eg. “HO112”)

•
In many formats (Excel, SAS, RDB, text)



Data Dictionary





110101

NCBI

Elements of Phenotype


Protocols, Questionnaires, Documentation



Data



Data Dictionary

•
Links Protocol element to Data column

•
Not generally available or widely usable



110101

NCBI

Organize Data First


Take Data in whatever format available


Automatically load columns and rows in Generic
Database


Automatically analyze content of columns


Review report with submitter

110101

NCBI

Organize Documents Next


Manually link specific questions/measures to Data
column names


Send out for tagging into XForms XML



View as HTML document


Process for indexing


Generate views of specific questions across forms
and studies


110101

NCBI

Identify Conflicts
Between Data and
Metadata

110101

NCBI

Enumerated

NOT HISPANIC


514

CHINESE


359

HISPANIC



27

TURKISH



20

SCOTTISH/IRISH


2

ITALIAN



2

AUSTRIAN/HUNGARIAN


1

SOUTH WEST NETHERLANDS


1

IRISH/CANADIAN INDIAN


1

PUERTO RICAN


1

SPANISH



1

HUNGARIAN



1

..(more)

110101

NCBI

NCBI WGA
–

What Can I Do?

•
[Unrestricted Public Use]

•
Browse/Search Projects and Studies

•
Browse/Search Protocols, Questionaires, Supporting
Documents

•
View Phenotype Measures Summary Data

•
View Genotype Measures Summary Data

•
Identify Studies of Interest and Authorization Authorities

•
View Pre
-
computed Associations [GAIN]


•
[Authorized Users Only]

•
Download Genotype/Phenotype Data for Individuals

110101

NCBI

Authorizing Use of Individual Data


Authorization for any study is done by the
sponsoring IC



Legacy studies may be governed by existing
consents but NIH may still move toward a trans
-
NIH policy on new studies



NCBI does not directly authorize anyone but only
acts on the IC’s behalf

110101

NCBI

Authentication is Done Centrally


Authentication (user account and login) is done
centrally through CIT.



Once authorized by different IC’s, user has a single
login and a single place to request and download
individual data from all studies to which they have
authorized access

110101

NCBI

Genotype Data


NCBI is working with ICs on Genotype Data where
possible


Both genotype calls and underlying intensity data
directly from vendors to NCBI


NCBI is working with major vendors on appropriate
data content and formats


Genotype summaries will be available to public as
permitted


Individual genotypes available through the same
authorization process as individual phenotypes

110101

NCBI

Automated Links from Genotype Probe

Linkage Disequilibrium

110101

NCBI

Current Activities


Genetic Association Information Network (GAIN)


Genetics and Environment Initiative (GEI)


Framingham Genetic Study


National Institute for Neurological Disease and
Stroke (NINDS)


NHGRI Medical Resequencing


NEI Macular Degeneration

110101

NCBI

GAIN


Run by Foundation for NIH


Currently accepting applications for clinical data
(due May 9)


Pfizer and Affymetrix paying for genotyping up to
seven studies (~1000 cases and controls) this year


Public metadata


Public “pre
-
computes”


Restricted access to phenotype/genotype data


Estimated public release of all data
–

late Summer


Future rounds of applications


110101

NCBI

Framingham Heart Study


Collaboration with NHLBI


Three generations of individuals from Framingham,
MA
–

15,000 people


Tens of thousands of variables


Extensive protocols and questionnaires

•
Already in the process of converting to XML

•
Data for one cohort just arriving


Access model

•
Public metadata

•
Private genotype/phenotype data

•
No “pre
-
computes”


110101

NCBI

NINDS Parkinsonism/Stroke


Four studies (more to follow)

•
Parkinsonism

•
Epilepsy

•
ALS

•
Stroke


Mostly categorical data


Access to Coriell cell lines for follow
-
up


Completely public access model


STR/pedigree data


Affy 100K data coming (but not public yet)

110101

NCBI

Closing the Loop