Literature Informatics August 20 , 2013

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Literature Informatics August 20 , 2013. Ansuman Chattopadhyay , PhD Head, Molecular Biology Information Service Health Sciences Library System University of Pittsburgh ansuman@pitt.edu http://www.hsls.pitt.edu/molbio. Ansuman Chattopadhyay , Ph.D. ansuman@pitt.edu. 1990-1996 - PowerPoint PPT Presentation

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Literature InformaticsAugust 20, 2013

Ansuman Chattopadhyay, PhDHead, Molecular Biology Information ServiceHealth Sciences Library SystemUniversity of Pittsburghansuman@pitt.edu

http://www.hsls.pitt.edu/molbio

•1990-1996University of Nebraska-LincolnPhD. in BiochemistryProtein synthesis initiation in eukaryotic system

•1997-2001Vanderbilt University School of Medicine, NashvilleResearch FellowEpidermal Growth Factor (EGF) mediated signal transduction

•2001-2002Cellomics Inc., PittsburghKnowledge Engineer

•2002- 2006Information Specialist in Molecular Biology and GeneticsHSLS, University of Pittsburgh

Ansuman Chattopadhyay, Ph.D.ansuman@pitt.edu

•2006- PresentHead, Molecular Biology Information ServiceHSLS, University of Pittsburgh

http://www.hsls.pitt.edu/molbio

•1993-2001SUNY Upstate Medical University, SyracusePhD in NeuroscienceSpecificity of connectivity in the mammalian olfactory system

•2001-2005Yale University School of Medicine, New HavenPostdoctoral FellowDevelopment & regeneration in the mammalian olfactory system

•2004-2006Southern Connecticut State University, New HavenMasters in Library Science

•2006- 2007Johns Hopkins Medical Institutions, Welch Medical Library, BaltimoreBasic Science Librarian

Carrie L Iwema, PhD, MLS, AHIP

iwema@pitt.edu

•2007- PresentUniversity of Pittsburgh, Health Sciences Library System, PittsburghInformation Specialist in Molecular Biology

http://www.hsls.pitt.edu/molbio

HSLS Molecular Biology Information Service

Workshops

Website

Software Licensing

Bioinformatics Consultations

http://www.hsls.pitt.edu/molbio

Today’s Agenda 10 am to 12 pm

Genes, Proteins and Literature Searching

1pm to 3 pm

NCBI Resources - Genetic Variations Databases

3pm to 3:30 pmQ A Session

Literature Informatics

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

Learn how to

.. find the most appropriate literature

.. mine the literature

.. manage your collected information

.. browse scientific papers

http://www.hsls.pitt.edu/molbio

Topics

Introduction Intuitive PubMed Search Next-Generation Literature Search

Tools Reference Management PDF Reader

http://www.hsls.pitt.edu/molbio

Literature Informatics

Comprehensive search: MESH term based PubMed Search PubMed special topics query

Next-generation literature search tools: GoPubMed, eTBlast Quertle HuGE Navigator Utopia Docs

http://www.hsls.pitt.edu/molbio

Introduction

Genomic achievements since the Human Genome Project

http://www.hsls.pitt.edu/molbio

Progress in Genomics1990 2003 2013

Time

Technology

6-8 year 3-4 months 2-3 days Time

1B 10-50 M 4-6 K

Cost Source: Eric Green; HGP10 Symposium

DNA Sequencing Cost

http://www.hsls.pitt.edu/molbio

Big DATA Biology

Single GeneSingle Protein

Single lab

Small Science

Multi-Gene System-wide

High-throughputMulti-Institution

Big Science

Growth of PubMed Citations

Lu et al. Database (Oxford). 2011: baq036

266 K

• Breast Cancer

104K • Schizophrenia

9.9K • BRCA1

67K . p53

Aug 20th 2013

http://www.hsls.pitt.edu/molbio

Searching PubMed

http://www.hsls.pitt.edu/molbio

Find published literature with statistical and numerical data on DENGUE OUTBREAKS in India.

What genes are reported to be associated with the disease SCHIZOPHRENIA?

http://www.hsls.pitt.edu/molbio

Citations: 20 millionJournals: 5200

Schizophrenia: 96,912Schizophrenia gene: 7382

Dengue outbreaks in India: 329 Dengue outbreaks statistics India: 21

http://www.hsls.pitt.edu/molbio

Challenges

Am I getting everything / the right things?

How to digest this?

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

Medical Subject Headings (MeSH)

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

The U.S. National Library of Medicine's controlled vocabulary (thesaurus)

Arranged in a hierarchical manner called the MeSH Tree Structures

Updated annually

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. OrganismsC. DiseasesD. Chemical and DrugsE. Analytical, Diagnostic and

Therapeutic Techniques and EquipmentF. Psychiatry and PsychologyG. Biological SciencesH. Physical SciencesI. Anthropology, Education,

Sociology and Social PhenomenaJ. Technology and Food and BeveragesK. Humanities L. Information Science M. Persons N. Health CareV. 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

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

MeSH Indexing

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

Find published literature with statistical and numerical data on DENGUE OUTBREAKS in India.

PubMed Query Using MeSH http://www.ncbi.nlm.nih.gov/mesh

http://www.hsls.pitt.edu/molbio

http://www.hsls.pitt.edu/molbio

Find articles on “Dengue outbreaks in India” by searching PubMed using MeSH terms

Link to the video tutorial:http://media.hsls.pitt.edu/media/clres2705/mesh.swf

Resources•Mesh Browser : http://www.ncbi.nlm.nih.gov/mesh

•PubMed: http://www.ncbi.nlm.nih.gov/pubmed

PubMed Query Using MeSH

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

PubMed Query Using MeSH

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

Building a PubMed Query

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

Building a PubMed Query

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

Building a PubMed Query

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

Building a PubMed Query

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

Building a PubMed Query

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

Building PubMed QueriesTerm Boolean Term Boolean Term # papersDengue AND Outbreaks 823Dengue * AND Outbreaks 746Dengue AND Outbreaks AND India 123Dengue* AND Outbreaks AND India 116Dengue AND Outbreaks/

statistics and numerical data

AND India 7

Dengue* AND Outbreaks/statistics and numerical data

AND India 7

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

Useful Links for MeSH

MESH Browser: http://www.ncbi.nlm.nih.gov/mesh 18 ways to improve your Pubmed searches by Carrie Iwema

http://bitesizebio.com/2008/03/05/18-ways-to-improve-your-pubmed-searches/

Searching by using the MeSH Database. NCBI Handbook : http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=helppubmed&part

=pubmedhelp#pubmedhelp.Searching_by_using_t

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

What genes are reported to be associated with the disease SCHIZOPHRENIA?

Topic-Specific PubMed Querieshttp://www.nlm.nih.gov/bsd/special_queries.html

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

http://www.hsls.pitt.edu/molbio

Find genes that are reported to be associated with the disease SCHIZOPHRENIA by searching PubMed

Link to the video tutorial:http://media.hsls.pitt.edu/media/clres2705/scz.swf

Resources•PubMed Clinical Queries: http://www.ncbi.nlm.nih.gov/pubmed/clinical

PubMed Special Topic Queries

http://www.hsls.pitt.edu/molbio

Search Filters

http://www.hsls.pitt.edu/molbio

PubMed Search Filter: Medical Genetics ("schizophrenia"[MeSH Terms] OR

"schizophrenia"[All Fields]) 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]))

http://www.hsls.pitt.edu/molbio

Topic-Specific PubMed Queries

PubMed Search Result Display

http://www.hsls.pitt.edu/molbio

How to digestthis?

Data Mining-Knowledge Discovery

http://www.hsls.pitt.edu/molbiohttp://www.hsls.pitt.edu/molbio

Next-Generation Literature Search Tools

GoPubMedQuertle

Latest Innovations in Literature Searching

GoPubMed Display search results sorted into meaningful topics and subtopics

http://www.hsls.pitt.edu/molbio

GoPubMed

http://www.hsls.pitt.edu/molbio

www.gopubmed.com

http://www.hsls.pitt.edu/molbio

Find genes that are reported to be associated with the disease SCHIZOPHRENIA by using GoPubMed

Link to the video tutorial:http://media.hsls.pitt.edu/media/clres2705/gopubmed.swf

Resources• GoPubMed: http://www.gopubmed.org/web/gopubmed/2?WEB10O00h00100090000

GoPubMed Search Result

http://www.hsls.pitt.edu/molbio

GoPubMed Search Result Analysis

http://www.hsls.pitt.edu/molbio

GoPubMed Search Result Analysis

http://www.hsls.pitt.edu/molbio

Latest Innovations in Literature Searching

http://www.hsls.pitt.edu/molbio

GoPubMed

Noteworthy links

GoPubMed: exploring PubMed with the Gene Ontology. Doms A,Schroeder M., Nucleic Acids Res. 2005 Jul 1; 33 (Web Server issue):W783-6. http://www.ncbi.nlm.nih.gov/pubmed/15980585

http://www.hsls.pitt.edu/molbio

PubMed driven Web Tools

http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/search/

http://www.hsls.pitt.edu/molbio

PubMed based Tools

http://www.hsls.pitt.edu/molbio

Lu et al. Database (Oxford). 2011; 2011: baq036

http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/search/

Extract gene list from Literature

http://www.hsls.pitt.edu/molbio

http://www.quertle.info/

Questions for Quertle

What genes cause Asthma? What cell lines are used in diabetes research? Which cell types are known to express EGFR? What animals are used in studies for diabetes? Which protein kinases activate TP53?

http://www.hsls.pitt.edu/molbio

http://www.hsls.pitt.edu/molbio

A short video on Quertle

Link to the video tutorial:http://media.hsls.pitt.edu/media/molbiovideos/quertle-ac0212.swf

Resources•Quertle: www.quertle.info

Search Engine for NIH funded research http://projectreporter.nih.gov/reporter.cfm

http://www.hsls.pitt.edu/molbio

NIH Grant Applications to Gene List

http://www.hsls.pitt.edu/molbio

PubMed

MESH GoPubMed Quertle

Search Engine for finding

Disease Causing Genes

Search Engine Just for Human GeneticsCDC HuGENavigator : http://hugenavigator.net/

http://www.hsls.pitt.edu/molbio

http://www.hsls.pitt.edu/molbio

Find human genes reported to be associated with Asthma

Find human SNPs reported to be associated with Asthma

Link to the video tutorial:http://media.hsls.pitt.edu/media/clres2705/asthma.swf

Resources• HugeNavigator: http://hugenavigator.net/HuGENavigator/home.do

GWAS Catalog http://www.ebi.ac.uk/fgpt/gwas/#timeseriestab

http://www.hsls.pitt.edu/molbio

Search Engine Just for Human Genetics

http://www.hsls.pitt.edu/molbio

Search Engine Just for Human GeneticsCDC HuGENavigator : http://hugenavigator.net/

http://www.hsls.pitt.edu/molbio

Search Engine Just for Human Geneticshttp://hugenavigator.net/HuGENavigator/huGEPedia.do

http://www.hsls.pitt.edu/molbio

Search Engine Just for Human GeneticsCDC HuGENavigator : http://hugenavigator.net/

http://www.hsls.pitt.edu/molbio

Find Disease Causing SNPs

What SNPs are associated with “Schizophrenia”?

http://hugenavigator.net/HuGENavigator/gWAHitStartPage.do

http://www.hsls.pitt.edu/molbio

Hands On

Search PubMed and retrieve a list of genes that can serve as biomarkers for Alzheimer Disease

Software for Finding Similar Text in Published Literature

Text-based Similarity Search Tools

Search Box:

http://www.hsls.pitt.edu/molbio

Text Similarity Search Tools

eTBLASThttp://etest.vbi.vt.edu/etblast3/

http://www.hsls.pitt.edu/molbio

Text Similarity Search Tools eTBLAST

http://www.hsls.pitt.edu/molbio

Text Similarity Search Tools

http://www.hsls.pitt.edu/molbio

Déjà Vu: a Database of Highly Similar Citationshttp://dejavu.vbi.vt.edu/dejavu/duplicate/

http://www.hsls.pitt.edu/molbio

Reference Management Tools

http://www.hsls.pitt.edu/molbio

Automated email Notification Tool

http://www.ncbi.nlm.nih.gov/sites/myncbi/Save your searches at My NCBI and set up an email notification on new publication based on your search query

http://www.hsls.pitt.edu/molbio

My NCBI1

23

http://www.hsls.pitt.edu/molbio

My NCBI

http://www.hsls.pitt.edu/molbio

4

My NCBI email Notification

http://www.hsls.pitt.edu/molbio

Reference Management Tools

Connotea

CiteULike

Mendaley

Zotero

online

downloadable

Scientific Research Papers

Web pages

EndNoteRefworks

http://www.hsls.pitt.edu/molbio

PDF Reader

http://www.hsls.pitt.edu/molbio

PDF Reader

Utopia.Docs ReadCube

NextGen PDF Reader: Utopia docs

http://www.hsls.pitt.edu/molbio

Utopia DocsPMID: 22683712

http://www.hsls.pitt.edu/molbio

Read a paper using Utopia.Docs

Link to the video tutorial:http://www.hsls.pitt.edu/molbio/videos/play?v=95

Resources• Utopia.Docs: http://getutopia.com/

READCUBE

READCUBE MEDIA FILE

Mendeley Utopia Docs

Search Engine for Life Scientists

http://www.hsls.pitt.edu/molbio

Molecular Databases

Nucleic Acids Research : Annual databases Issue NAR: Annual Web Server Issue Oxford Journal : Bioinformatics BioMedCentral: BMC Bioinformatics

http://www.hsls.pitt.edu/molbio

Growth of bioinformatics tools

Biomedical & Life Sciences Search Engines

OBRC : University of Pittsburghhttp://www.hsls.pitt.edu/molbio/obrc

Bioinformatics.cahttp://bioinformatics.ca/links_directory/

OReFil : University of Tokyohttp://orefil.dbcls.jp/

http://www.hsls.pitt.edu/molbio

Peptide Sequence >nxp|NX_P00533-1|EGFR|Epidermal growth factor receptor|Iso 1

MRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEV VLGNLEITYVQRNYDLSFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNMYYENSYALA VLSNYDANKTGLKELPMRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDF QNHLGSCQKCDPSCPNGSCWGAGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGC TGPRESDCLVCRKFRDEATCKDTCPPLMLYNPTTYQMDVNPEGKYSFGATCVKKCPRNYV VTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRKVCNGIGIGEFKDSLSINATNIKHFK NCTSISGDLHILPVAFRGDSFTHTPPLDPQELDILKTVKEITGFLLIQAWPENRTDLHAF ENLEIIRGRTKQHGQFSLAVVSLNITSLGLRSLKEISDGDVIISGNKNLCYANTINWKKL FGTSGQKTKIISNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECVDKCN LLEGEPREFVENSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVM GENNTLVWKYADAGHVCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVV ALGIGLFMRRRHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLRILKETEFKKIKVLGS GAFGTVYKGLWIPEGEKVKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGI CLTSTVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAA RNVLVKTPQHVKITDFGLAKLLGAEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSY GVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDVYMIMVKCWMIDADSRPK FRELIIEFSKMARDPQRYLVIQGDERMHLPSPTDSNFYRALMDEEDMDDVVDADEYLIPQ QGFFSSPSTSRTPLLSSLSATSNNSTVACIDRNGLQSCPIKEDSFLQRYSSDPTGALTED SIDDTFLPVPEYINQSVPKRPAGSVQNPVYHNQPLNPAPSRDPHYQDPHSTAVGNPEYLN TVQPTCVNSTFDSPAHWAQKGSHQISLDNPDYQQDFFPKEAKPNGIFKGSTAENAEYLRV

APQSSEFIGA

http://www.hsls.pitt.edu/molbio

Search for bioinformatics ResourcesLocate online tools that predict phosphorylation sites in a protein sequence.

Link to the video tutorial:http://media.hsls.pitt.edu/media/Search%20Bioinfo%20Resoursec.swf

Resources• Search.HSLS.MolBio :

Life Sciences Search Enginehttp://www.hsls.pitt.edu/molbio/

http://www.hsls.pitt.edu/molbio

Hands on

(a) Locate two online databases on microRNA targets, and report their URLs.

(b) Identify one database that store all HIV inhibiting siRNA data and cite its URL.

(c) Cite a paper offering a step-by-step guide

for analyzing ChIP-seq data.

Summary Construct a comprehensive PubMed query:

MESH Browser Retrieve gene/protein/disease information straight from a PubMed search :

GoPubmed, Quertle Find suitable journals for manuscript submission, etc… eTBLAST

Find disease causing genes and disease causing SNPs: HUGENavigator_ Geneprospector, Phenopedia, GWASIntegrator

Setup email alert for new publications My NCBI

Search for databases and software OBRC

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

Summary Setup email alert for new publications

My NCBI Search for databases and software

OBRC

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

Gene/Protein Information Mining

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

Bioinformatics Databases & Software Providers

National Center for Biotechnology Information (NCBI) Home page Site map Resource Guide

European Bioinformatics Institute (EBI) Home page Databases Software

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

Gene Information Gateways

o Open access resources:

National Center for Biotechnology Information (NCBI) Genbank Refseq

Entrez Gene Gene Expression Omnibus (GEO) OMIM

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

Protein Information Hubso Open access resources:

European Bioinformatics Institute (EBI)

Uniprot Interpro Prosite STRING

UCSC Genome Bioinformatics BLAT Search Gene Detail Page

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

Protein Information Hubso Open access resources:

National Center for Biotechnology Information (NCBI) Refseq Entrez Gene Conserved Domain Database (CDD) Molecular Modeling Database (MMDB) 3D structure viewer: Cn3D

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

Gene/Protein Information

Chromosomal location, mRNA, genomic seq, orthologs, paralogs, regulatory elements,

Amino acid seq, domain architecture, protein structure, post translational modifications

Gene expression, biological pathways, protein interaction map, disease association, biomarkers

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

Gene Questions ?

What is its function?

What are its neighboring genes?

What is its genomic seq?How many splice varients are there?What are its intron-exon architechure?

What diseases are associated with it?

Which tissues it expressed ?

How can I get its cDNA clone?

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

SNP

Genomic Sequence

Expression Profile

Interacting Partners3D Structure

mRNA Sequence

Chromosomal Localization

Disease

Amino acid Sequence

Homologous Sequences

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

NCBI : Entrez Gene

Entrez GeneFind: 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 a searchable database of genes, from RefSeq

genomes, and defined by sequence and/or located in the NCBI Map Viewer

Statistics Gene: 7974 organisms Genbank: 160,000 organisms

each record represents a single gene from a given organism

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

RefSeq Status Codes

Provisional Reviewed Predicted Genome Annotation

more about RefSeq status codes

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

Hands on

Find mRNA sequence for your gene of interest (p53, BRCA1, EGFR, PLCg1)

Start page: Entrez core nucleotide Use Limits, History and Preview Index

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

Video Tutorials

http://www.hsls.pitt.edu/molbio/videos?c=3

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

Find mRNA Sequence for Reelin Gene.

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

Gene FunctionWhat is its function?

Entrez Gene Page:

Summary (TOC)Gene OntologyGeneRIFsPathways (TOC)Biosystems (Links)

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

Gene Ontology (GO)

Controlled vocabulary tagging

• Function• Biological Processes• Cellular Component

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

Gene Ontology (GO) and KEGG GO

information page GO evidence codes

KEGG Information page

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

Function How many splice variants are there?What is/are its sequence?

Entrez Gene Page:

Genomic regions…(TOC)UCSC (Links)

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

Video Tutorials

Alternative Splicing

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

Intron-Exon CoordinatesWhat are its intron-exon architechure?

Entrez Gene Page:

DisplayChange it from Full report to Gene Table

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

Video Tutorials

Neighboring GenesWhat are its neighboring genes?

Entrez Gene Page:

Genomic context(TOC)

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

Video Tutorials

Chromosomal location

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

Associated DiseasesWhat diseases are associated with it? Entrez Gene Page:TOC

•General Information_Phenotype

LinksOMIMHuGE Navigator 

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

Video Tutorials

HomologeneWhat are its homologous genes?

Entrez Gene Page:

LinkHomologenechange Display settings

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

Video Tutorials

ReagentsHow can I get its cDNA clone?

..antibodies? .. siRNA ?

Entrez Gene Page:

TOC:Additional LinksResearch MateriasExact Antigen

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

Video Tutorials

Protein Information Gateways

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

UniprotKB : Universal Protein Resource : a comprehensive, centralized protein

information resource Developed by a consortium:

European Bioinformatics Institute (EBI) the Swiss Institute of Bioinformatics (SIB) the Protein Information Resource (PIR) Comprised of:

--Swiss-Prot: biologist-curated annotation data--TrEMBL: computationally annotation data--PIR-International Protein Sequence Database (PIR-PSD): the most

comprehensive and expertly-curated protein sequence database in the public domain for over 20 years.

Funded by: NIH, NSF, the European Union and the Swiss Federal government

Link to Wiki, YouTube, Blogs and Tweets: http://www.kosmix.com/topic/uniprot?

Tutorial Video: http://www.youtube.com/watch?v=TCF3qWn7siI&feature=youtube_gdata

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

Protein Questions ?

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

What is its Function?Amino acid sequence?

… molecular wt? isoelectric point (PI)? …post translational modifications? … presence of domain/pattern/profile? … hydrophobicity? … homologous orthologs? Etc.

Structure? … secondary and tertiary?

Interaction Partner?

Uniprot Video Tutorial

http://www.hsls.pitt.edu/molbio/videos/play?v=19

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

Protein Function from UniprotKB Uniprot Search:

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

Look under: general annotation_Function, ontologies_keywords, geneontology

Protein Sequence

Uniprot

• Sequence annotations

• sequences

Gene• Genomic regions,

transcripts, and products

• ccds (consensus cds report)

UCSC

• Sequence and links

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

Protein Sequence Analysis

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

PTM

• Uniprot• Seq annt

• IPA• Modificatio-ns

and Regulation

PI/MW

• Uniprot

• Seq_Tool• Compute PI

Hydroph-obicity

• Uniprot

• Seq_Tool• ProtScale

Peptide Digest

• Uniprot• Seq_Tools• PeptideMass• PeptideCutter

Homologous Seq

• Entrez Gene• Homologene

Domain/pattern• Uniprot• Sequence

annotation• InterPro• Entrez gene• Conserved

Domain

Protein Domain Resources

Protein Domain Databases:

InterPro

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

Protein Domains Wikipedia:

A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural domains. One domain may appear in a variety of evolutionarily related proteins. Domains vary in length from between about 25 amino acids up to 500 amino acids in length. The shortest domains such as zinc fingers are stabilized by metal ions or disulfide bridges. Domains often form functional units, such as the calcium-binding EF hand domain of calmodulin.

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Protein Domain: SH3 Src homology 3 domains; SH3 domains bind to proline-rich ligands

with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway

components and mediate multiprotein complex assemblies.

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Protein Structure

Primary

Secondary

Tertiary

Quarternary

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Useful links: http://www.kosmix.com/topic/protein_structure?

Taken from wikipedia

Protein Structure

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NCBI

Finding Protein Structure

PDB

Entrez Structure

NCBI BLINK via Entrez Gene/Protein

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Structure Databases and Viewer Databases:

RCSB Protein Data Bank (PDB) State University of New Jersey (Rutgers), the San Diego Supercomputer Center at the University of California San

Diego, the University of Wisconsin-Madison Link http://www.kosmix.com/topic/protein_data_bank?

MMDB NCBI's structure database is called MMDB (Molecular Modeling DataBase), and it is a

subset of three-dimensional structures obtained from the Protein Data Bank (PDB), excluding theoretical models..

Viewer: Cn3D :

a helper application for your web browser that allows you to view 3-dimensional structures from NCBI's Entrez retrieval service.

Rasmol: EBI First glance in j mol : A simple tool for macromolecular visualization. (More..)

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Protein Structure

Search for the 3D structure of P53 Entrez structure

View the crystal structure of mouse p53 core domain (MMDB: 42987) or Crystal Structure Of A P53 Core Dimer Bound To Dna ( PDB:2GEQ)

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Manipulating the Structure Viewer Window

Find Similar Structure: NCBI VAST

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NCBI BLink

BLink ("BLAST Link") displays the results of BLAST searches that have been done for every protein sequence in the Entrez Proteins data domain.

To access it, follow the BLink link displayed beside any hit in the results of an Entrez Proteins search.

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Hands-on Protein Structure

View the crystal structure of Chronophin (PDB entry: 2P69).

A variant of this protein with mutations in its amino acid sequence has been isolated. Can you predict any effect of its mutations into its function?

Hint: Find the amino acid residues which are in close contact (3.5 A) with PYRIDOXAL-5'-PHOSPHATE (PLP).

Label the amino acids and save the picture in PNG format. Learn more on Chronophin structure at:http://kb-dev.psi-structuralgenomics.org/KB/archives.jsp?pageshow=3

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Hands-on Protein Structure of Chronophin

http://kb-dev.psi-structuralgenomics.org/KB/archives.jsp?pageshow=3

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Sequence Alignment in Cn3D

NCBI

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Hands-On Can you identify the human protein which contains a

short peptide sequence: GPDGMPVIYHGHTLTTKIKFSDVLHTIKE ?

What is its function? What is its calculated PI and molecular wt? Which region of this protein is most hydrophobic? Locate five experimentally verified S/T/Y phosphorylation sites present in this

protein. Find the homologous mouse and fruit fly orthologs of this human protein and

report the % protein identity it shares with these orthologs. How many protein domains are reported to be present in this human protein? Find the location of its largest domain.

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Licensed Tools for Gene/Protein Information

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HSLS Licensed Tools

BioBase Metacore Ingenuity IPA

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Gene/Protein facts from Biobase

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http://goo.gl/9wpwG

BioBase BioKnowledge Library

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Protein Function from IPA

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Thank you!Any questions?

Ansuman Chattopadhyayansuman@pitt.edu

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