1. 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

2. Flow of transcriptomics analysis
2
healthy/disease
wt/KO
drug(+/-)
microarray NGS
raw data
intensity seq (contig)
normalization
genome mapping
tag count
t-test/ANOVA
hierarchical clustering
k-means
gene list
Need to interpret data by biological viewpoint
Statistics
No
biology!
?
What is biological features?
What is relationships to
initial conditions?

3. 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 media
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
BRCA1-A complex
BRCA1-BARD1 complex
gamma-tubulin ring complex
Cellular Component
Example) BRCA1 (Gene ID: 672)
Controlled vocabulary for representing biological features

4. GO assign and enrichment analysis
http://david.abcc.ncifcrf.gov/
TogoTV (Tutorial movie)
http://togotv.dbcls.jp/

5. 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 mediato
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
BRCA1-A complex
BRCA1-BARD1 complex
gamma-tubulin ring complex
nucleus
protein complex
Cellular Component
Example) BRCA1 (Gene ID: 672)
No information on
diseases and anatomy

6. MeSH terms
6
Medical Subject Headings
> 23,000 terms
Controlled vocabulary
15 categories
Disease,
Drugs,
Anatomy, ...
Gene MeSH
Article

7. X
OMIM ID
PMID
Gene/OMIM-
MeSH Pairs
Gene/OMIM-
PMID PairsPMID
OMIM ID
OMIM ID
PMID
Reference section
Corresponging
MeSH terms
PubMed
Search
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

8. 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

9. Differences and similarities
between type 1/2 diabetes
8
MeSH keywords
type1
diabetes
type2
diabetes
10e-10
10e-09
10e-08
10e-07
10e-06
10e-05
10e-04
10e-03
10e-02
0.05
0.10
0.20
0.30
0.40
0.50
0.75
1
p-value
Category
Diseases
Chemicals
and drugs
Anatomy
Diabetes Mellitus
Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2
Autoimmune Diseases
Insulin Resistance
Obesity
Insulin
Adiponectin
Pancreas
Spleen
Adipocytes

10. 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

11. Anguilla japonica
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SW
10
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Bioinformatics?
We are all molecular biologists
H2O
Na, K,
Cl, …
conc.
urine
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