Gendoo: Functional profiling of gene and disease features

for omics analysis

Research Organization of Information and Systems (ROIS)Database Center for Life Science (DBCLS),

NAKAZATO, Takeru

2014/7/4

NIG Retreat 2014

Flow of transcriptomics analysis

2

healthy/diseasewt/KO

drug(+/-)

microarray NGS

raw data

intensity seq (contig)

normalizationgenome mapping

tag count

t-test/ANOVAhierarchical clustering

k-means

gene list

Need to interpret data by biological viewpoint

Statistics

No

biology!

?

What is biological features?

What is relationships toinitial conditions?

Gene Ontology

DNA binding

androgen receptor binding

enzyme binding

transcription coactivator activity

tubulin binding

ubiquitin protein ligase binding

...

Molecular Function Biological Process

DNA damage response, signal transduction by p53 class mediator

resulting in transcription of p21 class mediator

G2 DNA damage checkpoint

androgen receptor signaling pathway

apoptotic process

cellular response to indole-3-methanol

chromosome segregation

double-strand break repair via homologous recombination

positive regulation of DNA repair

positive regulation of protein ubiquitination

postreplication repair

regulation of cell proliferation

regulation of transcription from RNA polymerase II promoter

regulation of transcription from RNA polymerase III promoter

response to DNA damage stimulus

response to estrogen stimulus

response to ionizing radiation

...

BRCA1-A complex

BRCA1-BARD1 complex

gamma-tubulin ring complex

nucleus

protein complex

ribonucleoprotein complex

ubiquitin ligase complex

Cellular Component

Example) BRCA1 (Gene ID: 672)

Controlled vocabulary for representing biological features

GO assign and enrichment analysishttp://david.abcc.ncifcrf.gov/

TogoTV (Tutorial movie)http://togotv.dbcls.jp/

Gene Ontology, ...

DNA binding

androgen receptor binding

enzyme binding

transcription coactivator activity

tubulin binding

ubiquitin protein ligase binding

...

Molecular Function Biological Process

DNA damage response, signal transduction by p53 class mediator

resulting in transcription of p21 class mediator

G2 DNA damage checkpoint

androgen receptor signaling pathway

apoptotic process

cellular response to indole-3-methanol

chromosome segregation

double-strand break repair via homologous recombination

positive regulation of DNA repair

positive regulation of protein ubiquitination

postreplication repair

regulation of cell proliferation

regulation of transcription from RNA polymerase II promoter

regulation of transcription from RNA polymerase III promoter

response to DNA damage stimulus

response to estrogen stimulus

response to ionizing radiation

...

BRCA1-A complex

BRCA1-BARD1 complex

gamma-tubulin ring complex

nucleus

protein complex

ribonucleoprotein complex

ubiquitin ligase complex

Cellular Component

Example) BRCA1 (Gene ID: 672)

No information on

diseases and anatomy

MeSH terms

6

Medical Subject Headings

> 23,000 terms

Controlled vocabulary

15 categories

Disease, Drugs, Anatomy, ...

Gene MeSH

Article

X

OMIM ID

PMID

Gene/OMIM-MeSH Pairs

Gene/OMIM-PMID PairsPMID

OMIM ID

OMIM ID

PMIDReference section

CorrespongingMeSH terms

PubMedSearch

Step 3: Collect PMIDs assigned by MeSH terms corresponding to genes and diseases

Step 2: Collect Entrez Gene/OMIM IDs described in MEDLINE articles

Step 1: Extract PMIDs cited in Entrez Gene/OMIM reference sections

Scoring

p-value

MeSH keywords related to BRCA1

7

Example) BRCA1 (Gene ID: 672)

Breast Neoplasms

Ovarian Neoplasms

BRCA1 Protein

Tumor Suppressor Proteins

Rad51 Recombinase

Breast

Chromosomes, Human, Pair 17

0

0

0

5.91 × 10-136

1.66 × 10-54

1.52 × 10-43

9.03 × 10-23

Disease

Chemicals and Drugs

Anatomy

MeSH Terms Category p-value

Differences and similarities between type 1/2 diabetes

8

MeSH keywords type 1

diabe

tes

type 2

diabe

tes

10e-1010e-0910e-0810e-0710e-0610e-0510e-0410e-0310e-020.050.100.200.300.400.500.751

p-valueCategory

Diseases

Chemicalsand drugs

Anatomy

Diabetes MellitusDiabetes Mellitus, Type 1Diabetes Mellitus, Type 2

Autoimmune DiseasesInsulin Resistance

ObesityInsulin

AdiponectinPancreas

SpleenAdipocytes

Implementation

9

http://gendoo.dbcls.jp/

Reference: Gendoo: Functional profiling of gene and disease features using MeSH vocabulary. Nucleic Acids Res, 37 (Suppl. 2), 2009. PMID: 19498079

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