9 th June 2009
Ansuman Chattopadhyay, PhD
Head, Molecular Biology Information Services
Health Sciences Library System
University of Pittsburgh ansuman@pitt.edu
http://www.hsls.pitt.edu/guides/genetics

Goals




HSLS Molecular Biology
Information Service
Literature searching tools
Gene-centered databases
DNA and Protein analysis tools http://www.hsls.pitt.edu/guides/genetics

My Background
1991-1996: University of Nebraska, Lincoln
PhD: Biochemistry, Protein Synthesis
1996-2000: Vanderbilt University School of
Medicine, Nashville, Cancer Biology
2000-2001: Cellomics Inc. Pittsburgh,
Bioinformatics
2002-2008: HSLS, University of Pittsburgh,
Molecular Biology Information service http://www.hsls.pitt.edu/guides/genetics

Molecular Biology in the Library







University of Washington, Health Sciences Library
University of Pittsburgh, Falk Library
Harvard Medical School, Countway Medical Library
Washington University , Bernard Becker Medical
Library
University of Florida, Health Sciences Center Library
University of Southern California , Norris Medical
Library
Stanford University, Lane Medical Library http://www.hsls.pitt.edu/guides/genetics

Information Overload
5,200
Journals
197K • Breast Cancer
82K • Schizophrenia
6.4K
• BRCA1
48 K • p53 http://www.hsls.pitt.edu/guides/genetics

Sequence Based Information http://www.hsls.pitt.edu/guides/genetics

In silico Support
Literature
Search
Sequence
Analysis
Omics
Data
Analysis http://www.hsls.pitt.edu/guides/genetics

http://www.hsls.pitt.edu/guides/genetics

Literature Informatics
 US National Library of Medicine (NLM) Medline
Database
 Medical Subject Heading
 PubMed Based Literature Informatics Tools

ClusterMed

GoPubMed

NovoSeek

EtBlast
PubMed
MESH
Database
ClusterMed
GoPubMed http://www.hsls.pitt.edu/guides/genetics

PubMed (http://pubmed.gov)
MEDLINE is the largest component of PubMed the freely accessible online database of biomedical journal citations and abstracts created by the U.S. National Library of Medicine
(NLM®).
5,200 journals published in the United States and more than 80 other countries
Contains citations indexed 1949 to the present .
http://www.hsls.pitt.edu/guides/genetics

PubMed Search Stats http://www.hsls.pitt.edu/guides/genetics

PubMed Display: Abstract Plus http://www.hsls.pitt.edu/guides/genetics

PubMed Display: Medline http://www.hsls.pitt.edu/guides/genetics

Medical Subject Headings (MeSH)
The U.S. National Library of
Medicine's controlled vocabulary (thesaurus)
Arranged in a hierarchical manner called the MeSH Tree
Structures
Updated annually http://www.hsls.pitt.edu/guides/genetics

MeSH Vocabulary


Headings over 24,000 representing concepts found in the biomedical literature (Body Weight, Kidney, Radioactive Waste)


Subheadings attached to headings to describe a specific aspect of a concept
(adverse effects , metabolism, diagnosis, therapy)


Supplementary Concept Records over 172,000 terms in a separate chemical thesaurus -updated weekly (cordycepin , valspodar , tacrolimus binding protein 4)
 Publication Types
(Letter, Review, Randomized Controlled Trial) http://www.hsls.pitt.edu/guides/genetics

MeSH Tree Structure



A. Anatomy
B. Organisms
C. Diseases
D. Chemical and Drugs
E. Analytical, Diagnostic and
Therapeutic Techniques and Equipment
F. Psychiatry and Psychology
G. Biological Sciences
H. Physical Sciences
I. Anthropology, Education,
Sociology and Social Phenomena
J. Technology and Food and Beverages
K. Humanities
L. Information Science
M. Persons
N. Health Care
V. Publication Characteristics
Z. Geographic Locations http://www.hsls.pitt.edu/guides/genetics

MeSH Indexing http://www.hsls.pitt.edu/guides/genetics
Source: NLM

MeSH Indexing
Genes/Chemicals
MeSH Terms http://www.hsls.pitt.edu/guides/genetics

PubMed Search
 Retrieve published articles on

Dengue outbreaks

Dengue outbreaks in India

Dengue outbreaks outside India including

Statistical and numerical data on dengue outbreaks http://www.hsls.pitt.edu/guides/genetics

PubMed Search: Dengue Outbreaks
1 http://www.ncbi.nlm.nih.gov/mesh?itool=sidebar http://www.hsls.pitt.edu/guides/genetics

PubMed Search: Dengue Outbreaks
MESH DATABASE
2
Dengue http://www.hsls.pitt.edu/guides/genetics

PubMed Search: Building Query http://www.hsls.pitt.edu/guides/genetics

PubMed Search: Building Query http://www.hsls.pitt.edu/guides/genetics

PubMed Search: Building Query
5
3
4 http://www.hsls.pitt.edu/guides/genetics

PubMed Search: Building Query
6 http://www.hsls.pitt.edu/guides/genetics

PubMed Search: Building Query
7 http://www.hsls.pitt.edu/guides/genetics

PubMed Search: Building Query
9
8 http://www.hsls.pitt.edu/guides/genetics

PubMed Search: Building Query
10 http://www.hsls.pitt.edu/guides/genetics

PubMed Search: Building Query http://www.hsls.pitt.edu/guides/genetics

PubMed Search: Building Query
Term
Dengue
Dengue
Dengue
Dengue
Boolean
AND
AND
AND
AND
Term Boolean Term outbreaks outbreaks AND outbreaks NOT
Outbreaks/
Statistics and numerical data
India
India
# of
Papers
687
109
578
82 http://www.hsls.pitt.edu/guides/genetics

Search Result Clustering http://www.hsls.pitt.edu/guides/genetics

Search Result Clustering http://clusty.com
http://www.hsls.pitt.edu/guides/genetics

Vivisimo ClusterMed http://demos.vivisimo.com/vivisimo/cgi-bin/query-meta?v:frame=form&frontpage=1&v:project=clustermed http://www.hsls.pitt.edu/guides/genetics

Query Details
Dengue AND Outbreaks AND India 109 http://www.hsls.pitt.edu/guides/genetics

ClusterMed
Topics http://www.hsls.pitt.edu/guides/genetics

Clustering in PubMed: ClusterMed
 organizes the long list of results returned by PubMed into hierarchical folders with meaningful categories, allowing researchers to hone in on the most relevant results quickly.
 does this on-the-fly without requiring any preprocessing, using terms taken from the brief descriptions in the search results.
 with the folders, users can discover themes, view related articles, and drill down from the topic hierarchy http://www.hsls.pitt.edu/guides/genetics

Topical Clusters
Institutions
Authors
Pub Dates http://www.hsls.pitt.edu/guides/genetics

GoPubMed Developed by Transinsight http://www.gopubmed.com
/ http://www.hsls.pitt.edu/guides/genetics

GoPubMed
Dengue AND Outbreaks NOT India 578 http://www.hsls.pitt.edu/guides/genetics

GoPubMed
Authors
Journals
Pub Dates
Dengue AND Outbreaks NOT http://www.hsls.pitt.edu/guides/genetics
India 578

PubMed Advanced Search http://www.hsls.pitt.edu/guides/genetics

Literature Search Workflow
ClusterMed
PubMed
MESH
Database
GoPubMed http://www.hsls.pitt.edu/guides/genetics

PubMed Query with Boolean
 Retrieve articles focused on molecular genetics of Schizophrenia published in past five years :
 ("schizophrenia"[Majr] AND (("genetics, medical"[MeSH Terms] OR
("genetics"[All Fields] AND "medical"[All Fields]) OR "medical genetics"[All Fields] OR ("medical"[All Fields] AND "genetics"[All
Fields])) OR ("genotype"[MeSH Terms] OR "genotype"[All Fields])
OR "genetics"[Subheading] AND ("genetics"[Subheading] OR
"genetics"[All Fields] OR "genetics"[MeSH Terms])) AND
("2004/03/13"[PDat] : "2009/03/11"[PDat]) http://www.hsls.pitt.edu/guides/genetics

Research on Optimal Search Strategies http://www.hsls.pitt.edu/guides/genetics

PubMed Pre-Build Queries http://www.ncbi.nlm.nih.gov/entrez/query/static/clinical.shtml
http://www.hsls.pitt.edu/guides/genetics

PubMed Query with Boolean
 Retrieve articles focused on molecular genetics of Schizophrenia published in past five years:
 ( "schizophrenia"[Majr] AND (("genetics, medical"[MeSH Terms] OR ("genetics"[All Fields] AND
"medical"[All Fields]) OR "medical genetics"[All Fields] OR ("medical"[All Fields] AND
"genetics"[All Fields])) OR ("genotype"[MeSH Terms] OR "genotype"[All Fields]) OR
"genetics"[Subheading] AND ("genetics"[Subheading] OR "genetics"[All Fields] OR
"genetics"[MeSH Terms])) AND ("2004/03/13"[PDat] : "2009/03/11"[PDat]) http://www.hsls.pitt.edu/guides/genetics

GoPubMed Analysis http://www.hsls.pitt.edu/guides/genetics

GoPubMed Search Result Statistics http://www.hsls.pitt.edu/guides/genetics

Go PubMed Authors Network http://www.hsls.pitt.edu/guides/genetics

GoPubMed World Map of Publications http://www.hsls.pitt.edu/guides/genetics


My NCBI: an Automated email
Notification Tool
Save your searches at MyNCBI and set up an email notification on new publication based on your search query http://www.hsls.pitt.edu/guides/genetics

My NCBI
3
2 http://www.hsls.pitt.edu/guides/genetics
1

My NCBI
4 http://www.hsls.pitt.edu/guides/genetics

NovoSeek : a Search Engine for Biomedical
Literature in Medline and US Grants http://www.hsls.pitt.edu/guides/genetics

NovoSeek Search: Alzheimer Clinical Trials http://www.hsls.pitt.edu/guides/genetics

Literature Search Workflow
Authors
R
A
T
U
R
E
L
I
T
E
Global Map
Topics
Authors Networks
S
E
A
R
C
H
Journals Genes http://www.hsls.pitt.edu/guides/genetics

eTBLAST
 Visualize Related Articles
 Find an Expert in this Field
 Find a Journal for your Manuscript
 View the Publication History of this Topic http://www.hsls.pitt.edu/guides/genetics

eTBLAST http://www.hsls.pitt.edu/guides/genetics

eTBLAST Analysis http://www.hsls.pitt.edu/guides/genetics

eTBLAST Analysis on Scientific Papers http://www.hsls.pitt.edu/guides/genetics

Growth of Molecular Databases and Software
Related Publications in PubMed http://www.hsls.pitt.edu/guides/genetics
Source: Nodal Point Blog

Molecular Databases
 Nucleic Acids Research: Oxford Journals

Annual databases Issue

Annual Web Server Issue
 Journals

Bioinformatics

BMC Bioinformatics
 Articles on molecular databases

ClusterMed search : 3196 http://www.hsls.pitt.edu/guides/genetics

Growth of Molecular Databases
2008:1078
2008: 1078 http://www.hsls.pitt.edu/guides/genetics
Source: Nodal Point Blog

Molecular Databases Catalog
HSLS
OBRC
1768 links to databases and software
~2050 hits/day http://www.hsls.pitt.edu/guides/genetics

HSLS OBRC http://www.hsls.pitt.edu/guides/genetics

HSLS OBRC http://www.hsls.pitt.edu/guides/genetics

HSLS OBRC http://www.hsls.pitt.edu/guides/genetics

Search.HSLS.MolBio
 Integrated search system

Databases & Software

Articles on Databases & Software

Genes/Proteins

Pathways

Protocols

Recommended Articles
 Tabbed browsing
 Clustered search results http://www.hsls.pitt.edu/guides/genetics

Search.HSLS.MolBio
http://www.hsls.pitt.edu/guides/genetics

Molecular Databases and Software: protein structure prediction http://www.hsls.pitt.edu/guides/genetics

Molecular Databases and Software:
Sumoylation http://www.hsls.pitt.edu/guides/genetics

Genes/Proteins Info http://www.hsls.pitt.edu/guides/genetics

Entrez Gene http://www.hsls.pitt.edu/guides/genetics

Genes/Proteins Info: p53 http://www.hsls.pitt.edu/guides/genetics

Clustering by Organisms http://www.hsls.pitt.edu/guides/genetics

Search pathways:p53 http://www.hsls.pitt.edu/guides/genetics

Protocols: http://www.hsls.pitt.edu/guides/genetics

Search protocols for microarray data analysis http://www.hsls.pitt.edu/guides/genetics

Recommended Articles http://www.hsls.pitt.edu/guides/genetics

Recommended Articles http://www.hsls.pitt.edu/guides/genetics

Hands-on exercise
 Locate databases on


Natural antisense, UTR , copy number variation
Sumoylation, phosphorylation
 Retrieve gene information for

Your favorite gene or BRCA1 or BAD
 Find a suitable protocol for experiments:



Real time PCR , methylation PCR , CGH array
Multiple sequence alignment , BLAST search
Protein structure prediction http://www.hsls.pitt.edu/guides/genetics

HSLS Mol Bio Homepage Hits
Hits /Day
2853
1576
1027
329
2003
439
523
2004 2005 2006 http://www.hsls.pitt.edu/guides/genetics
2007 2008

http://www.hsls.pitt.edu/guides/genetics

HSLS Molecular Biology Information Service
Workshops
Bioinformatics
Consultations
Software
Licensing http://www.hsls.pitt.edu/guides/genetics
Website

HSLS Licensed Bioinformatics
Resources http://www.hsls.pitt.edu/guides/genetics

HSLS Licensed Tools http://www.hsls.pitt.edu/guides/genetics

Pathway Drawing Tool: PathwayBuilder http://www.hsls.pitt.edu/guides/genetics

Pathway Drawing Tool: PathwayBuilder http://www.hsls.pitt.edu/guides/genetics

HSLS Licensed Tools http://www.hsls.pitt.edu/guides/genetics

VectorNTI http://www.hsls.pitt.edu/guides/genetics

Sequencher http://www.hsls.pitt.edu/guides/genetics

HSLS Licensed Tools http://www.hsls.pitt.edu/guides/genetics

Microarray Data Analysis raw data
GeneSpring
Statistical packages
Gene List
Literature findings
Biology
• Ingenuity IPA
• GeneGO Metacore
• PathwayArchitect
• Explain http://www.hsls.pitt.edu/guides/genetics

Omics Tools
Control
A549 cell
+
Ethanol (25 m mol/L) 48 hr http://www.hsls.pitt.edu/guides/genetics
Treated
A549 cell
+
Resveratrol (25 m mol/L) 48 hr

Gene Expression Databases
NCBI
• Gene Expression Omnibus
(GEO)
EBI
• ArrayExpress http://www.hsls.pitt.edu/guides/genetics

Raw data processing : ArrayAssist http://www.hsls.pitt.edu/guides/genetics

Microarray Data Processing: ArrayAssist
Workflow: http://www.hsls.pitt.edu/guides/genetics

Microarray Processed Data http://www.hsls.pitt.edu/guides/genetics

Discovery Step: Pathway Analysis
Gene List
Ingenuity
IPA
GeneGo
Metacore
Biobase
ExPlain http://www.hsls.pitt.edu/guides/genetics

Common Functions and Pathways: IPA
Analysis http://www.hsls.pitt.edu/guides/genetics

Common Functions and Pathways: IPA
Analysis http://www.hsls.pitt.edu/guides/genetics

Common Pathways: IPA http://www.hsls.pitt.edu/guides/genetics

Pathway Map: p53 http://www.hsls.pitt.edu/guides/genetics

Pathway Map: NFkB and TGF beta http://www.hsls.pitt.edu/guides/genetics

Interaction Map: IPA http://www.hsls.pitt.edu/guides/genetics

Interaction Map with Data Overlay: IPA http://www.hsls.pitt.edu/guides/genetics

Pathway Analysis: GeneGo Metacore http://www.hsls.pitt.edu/guides/genetics

Metacore: Analyze Network (receptors)
C-Myc p53

Pathway Analysis: GeneGo Metacore http://www.hsls.pitt.edu/guides/genetics

Promoter Analysis: BioBase Explain
 Over representation of TF binding sites http://www.hsls.pitt.edu/guides/genetics

BioBase Explain: Key Molecules Prediction
Key Molecules
Over representation of
TF Binding site
Promoter http://www.hsls.pitt.edu/guides/genetics
Microarray

Use of Ingenuity, GeneGO and BioBase
 DNA microarrays
 Protein arrays
 CHIP-chip
 Search for

Gene/protein info (human, mouse, rat, yeast)

Drug/small molecule

Disease info

Promoter sequences

Transcription factors binding sites http://www.hsls.pitt.edu/guides/genetics

Gene Regulation: Transfac and
TransPro http://www.hsls.pitt.edu/guides/genetics

HSLS Molecular Biology Information Service
Workshops
Bioinformatics
Consultations
Software
Licensing http://www.hsls.pitt.edu/guides/genetics
Website

HSLS Bioinformatics Workshops http://www.hsls.pitt.edu/guides/genetics
Online PPT

Bioinformatics FAQ: How Do I?
http://www.hsls.pitt.edu/guides/genetics

http://www.hsls.pitt.edu/guides/genetics

Bioinformatics Databases & Software Providers
 NCBI

Home page

Site map

Resource Guide
 EBI

Home page

Databases

Software http://www.hsls.pitt.edu/guides/genetics

US NCBI Databases http://www.hsls.pitt.edu/guides/genetics

NCBI sequence databases
 GenBank
 archival database of nucleotide sequences from >160,000 organisms More info
 GenPept
 conceptual translation of GenBank CDS
 Refseq
 based on GenBank record, non-redundant expert verified databases of reference sequences http://www.hsls.pitt.edu/guides/genetics

International Nucleotide Sequence
Database Collaboration http://www.hsls.pitt.edu/guides/genetics

Primary Vs Derivative databases http://www.hsls.pitt.edu/guides/genetics

RefSeq Scope & Accessions
 Genomic DNA



NC_123456 - complete genome, complete chromosome, complete plasmid
NG_123456 - genomic region
NT_123456 - genomic contig
 mRNA NM_123456
 Protein - NP_123456
 more about RefSeq scope and accessions... http://www.hsls.pitt.edu/guides/genetics

Entrez Gene
 a searchable database of genes, from RefSeq genomes, and defined by sequence and/or located in the NCBI Map Viewer
 Statistics


Gene: 4818 organisms
Genbank: 160,000 organisms
 each record represents a single gene from a given organism http://www.hsls.pitt.edu/guides/genetics

US NCBI : Entrez Gene
Chromosomal
Localization
Genomic
Sequence mRNA Sequence
Amino acid
Sequence
Homologous
Sequences
Expression
Profile
3D Structure
Interacting
Partners
Disease SNP http://www.hsls.pitt.edu/guides/genetics

Entrez Gene
Find:

 gene symbols and aliases sequences: genomic, mRNA, protein


 intron-exon architecture genomic context: neighboring and antisense genes
Interacting partners
 associated gene ontology terms: function, cellular component and biological process http://www.hsls.pitt.edu/guides/genetics

Entrez Gene search
 Query: BRCA1
 Search Tips:

Query text box: BRCA1
 Limits:

 select: “Gene name” from drop-down menu
Limit by taxonomy: select “Homo sapiens” http://www.hsls.pitt.edu/guides/genetics

Alternative Splicing http://www.hsls.pitt.edu/guides/genetics

Gene Ontology ( GO )

Controlled vocabulary tagging
•
•
•
http://www.hsls.pitt.edu/guides/genetics

Sample Exercises
 Find intron-exon coordinates for your favorite gene
 What are the genes involved in the disease phenylketonuria in humans?
 From where you can order cDNA clone for the human
PAH gene?
 How many splice variants have been reported for human EGFR gene?
 What is the genomic sequence for mouse muscle protein titin?
http://www.hsls.pitt.edu/guides/genetics

Gene-centered open access resources: beyond NCBI & EBI
 Weizmann Institute of Science : GeneCards
 UCSC genome bioinformatics:

UCSC gene page

UCSC BLAT


How do I?
identify a short nucleotide fragment and determine its corresponding protein sequence?
http://www.hsls.pitt.edu/guides/genetics

HSLS licensed Gene-centered Resources
 Ingenuity IPA : Ingenuity Systems

Expert extracted gene focused knowledgebase
 Metacore : GeneGo

Human curated gene-based knowledge library
 Protein Lounge

Biological pathway database
 Biobase Knowledge Library

Promoter sequence database
 Transfac http://www.hsls.pitt.edu/guides/genetics

Hands-on exercise:
 Take your favorite gene or p53 (human) as a search term and
 find its promoter sequence
 identify transcription factors which could bind its regulatory region
 find its upstream regulators and report supporting citations http://www.hsls.pitt.edu/guides/genetics

Any questions?
Carrie Iwema iwema@pitt.edu
412-383-6887
Ansuman Chattopadhyay ansuman@pitt.edu
412-648-1297 http://www.hsls.pitt.edu/guides/genetics