literature informatics august 20 , 2013

Literature InformaticsAugust 20, 2013

Ansuman Chattopadhyay, PhDHead, Molecular Biology Information ServiceHealth Sciences Library SystemUniversity of [email protected]

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

mailto:[email protected]


•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, [email protected]

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





•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

[email protected]

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



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

HSLS Molecular Biology Information Service

Workshops

Website

Software Licensing

Bioinformatics Consultations



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



Learn how to

.. find the most appropriate literature

.. mine the literature

.. manage your collected information

.. browse scientific papers




Topics

Introduction Intuitive PubMed Search Next-Generation Literature Search

Tools Reference Management PDF Reader




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




Introduction

Genomic achievements since the Human Genome Project




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


http://www.youtube.com/playlist?list=PL1ay9ko4A8slWhqrCPupJ3GRPRp6bGiE8

DNA Sequencing Cost




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




Searching PubMed




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

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




Citations: 20 millionJournals: 5200

Schizophrenia: 96,912Schizophrenia gene: 7382

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




Challenges

Am I getting everything / the right things?

How to digest this?



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


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)



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



MeSH Indexing


Source: NLM


MeSH Indexing



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.ncbi.nlm.nih.gov/mesh



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


http://media.hsls.pitt.edu/media/clres2705/mesh.swf


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

PubMed Query Using MeSH



Building a PubMed Query



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



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.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=helppubmed&part=pubmedhelp

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=helppubmed&part=pubmedhelp


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.nlm.nih.gov/bsd/special_queries.html



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


http://media.hsls.pitt.edu/media/clres2705/scz.swf

http://www.ncbi.nlm.nih.gov/pubmed/clinical

PubMed Special Topic Queries



Search Filters



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]))



Topic-Specific PubMed Queries

PubMed Search Result Display


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



GoPubMed


www.gopubmed.com


http://www.gopubmed.com/


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


http://media.hsls.pitt.edu/media/clres2705/gopubmed.swf

http://www.gopubmed.org/web/gopubmed/2?WEB10O00h00100090000

GoPubMed Search Result



GoPubMed Search Result Analysis



Latest Innovations in Literature Searching



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.ncbi.nlm.nih.gov/pubmed/15980585


PubMed driven Web Tools

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




PubMed based Tools


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





Extract gene list from Literature


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?




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


http://media.hsls.pitt.edu/media/molbiovideos/gquertle-ac0212.swf


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


http://projectreporter.nih.gov/reporter.cfm


NIH Grant Applications to Gene List



PubMed

MESH GoPubMed Quertle

Search Engine for finding

Disease Causing Genes

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


http://hugenavigator.net/



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


http://media.hsls.pitt.edu/media/clres2705/asthma.swf

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

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


http://www.ebi.ac.uk/fgpt/gwas/


Search Engine Just for Human Genetics



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


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


Find Disease Causing SNPs

What SNPs are associated with “Schizophrenia”?

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


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


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:



Text Similarity Search Tools

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


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


Text Similarity Search Tools eTBLAST



Text Similarity Search Tools



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


http://dejavu.vbi.vt.edu/dejavu/duplicate/


Reference Management Tools



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.ncbi.nlm.nih.gov/sites/myncbi/


My NCBI1

23



My NCBI


4


My NCBI email Notification



Reference Management Tools

Connotea

CiteULike

Mendaley

Zotero

online

downloadable

Scientific Research Papers

Web pages

EndNoteRefworks



PDF Reader




PDF Reader

Utopia.Docs ReadCube

NextGen PDF Reader: Utopia docs



Utopia DocsPMID: 22683712


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/


http://www.hsls.pitt.edu/molbio/videos/play?v=95

http://getutopia.com/

READCUBE

READCUBE MEDIA FILE

Mendeley Utopia Docs

Search Engine for Life Scientists



Molecular Databases

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


Growth of bioinformatics tools

http://nar.oxfordjournals.org/content/vol36/suppl_1/index.dtl

http://nar.oxfordjournals.org/content/vol35/suppl_2/index.dtl

http://bioinformatics.oxfordjournals.org/

http://www.biomedcentral.com/bmcbioinformatics/

http://www.biomedcentral.com/bmcbioinformatics/


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/guides/genetics/obrc

http://bioinformatics.ca/links_directory/



http://orefil.dbcls.jp/


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


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 :


http://media.hsls.pitt.edu/media/Search%20Bioinfo%20Resoursec.swf

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



Summary Setup email alert for new publications

My NCBI Search for databases and software

OBRC



Gene/Protein Information Mining


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.ncbi.nlm.nih.gov/

http://www.ncbi.nlm.nih.gov/Sitemap/AlphaList.html

http://www.ncbi.nlm.nih.gov/Sitemap/ResourceGuide.html

http://www.ebi.ac.uk/

http://www.ebi.ac.uk/Databases/

http://www.ebi.ac.uk/Tools/

Gene Information Gateways

o Open access resources:

National Center for Biotechnology Information (NCBI) Genbank Refseq

Entrez Gene Gene Expression Omnibus (GEO) OMIM



Protein Information Hubso Open access resources:

European Bioinformatics Institute (EBI)

Uniprot Interpro Prosite STRING

UCSC Genome Bioinformatics BLAT Search Gene Detail Page



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



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


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?


SNP

Genomic Sequence

Expression Profile

Interacting Partners3D Structure

mRNA Sequence

Chromosomal Localization

Disease

Amino acid Sequence

Homologous Sequences


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



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.ncbi.nlm.nih.gov/RefSeq/

http://www.ncbi.nlm.nih.gov/projects/Gene/gentrez_stats.cgi


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.ncbi.nlm.nih.gov/Sitemap/ResourceGuide.html


International Nucleotide Sequence Database Collaboration



Primary Vs Derivative databases



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.ncbi.nlm.nih.gov/RefSeq/key.html



RefSeq Status Codes

Provisional Reviewed Predicted Genome Annotation

more about RefSeq status codes




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.ncbi.nlm.nih.gov/sites/entrez


Sequence Format

GenBank Header Features Sequence

FASTA Sequence

Example: U49845 Sample GenBank record Sequence Revision History tool


http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=nuccore&term=U49845%5Bpacc%5D&doptcmdl=GenBank

http://www.ncbi.nlm.nih.gov/Sitemap/samplerecord.html



http://www.ncbi.nlm.nih.gov/Sitemap/sequencerevisionhistory.html

http://www.ncbi.nlm.nih.gov/Sitemap/sequencerevisionhistory.html


Video Tutorials

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


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


Find mRNA Sequence for Reelin Gene.



Gene FunctionWhat is its function?

Entrez Gene Page:

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



Gene Ontology (GO)

Controlled vocabulary tagging

• Function• Biological Processes• Cellular Component


http://www.geneontology.org/


Gene Ontology (GO) and KEGG GO

information page GO evidence codes

KEGG Information page


http://www.kosmix.com/topic/gene_ontology?

http://www.geneontology.org/GO.evidence.shtml

http://www.kosmix.com/topic/Kyoto_Encyclopedia_of_Genes_and_Genomes?


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

Entrez Gene Page:

Genomic regions…(TOC)UCSC (Links)


Video Tutorials


Alternative Splicing



Intron-Exon CoordinatesWhat are its intron-exon architechure?

Entrez Gene Page:

DisplayChange it from Full report to Gene Table


Video Tutorials


Neighboring GenesWhat are its neighboring genes?

Entrez Gene Page:

Genomic context(TOC)


Video Tutorials


Chromosomal location



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

•General Information_Phenotype

LinksOMIMHuGE Navigator


Video Tutorials


HomologeneWhat are its homologous genes?

Entrez Gene Page:

LinkHomologenechange Display settings


Video Tutorials


ReagentsHow can I get its cDNA clone?

..antibodies? .. siRNA ?

Entrez Gene Page:

TOC:Additional LinksResearch MateriasExact Antigen


Video Tutorials


Protein Information Gateways



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.kosmix.com/topic/uniprot?

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

Protein Questions ?


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





Protein Function from UniprotKB Uniprot Search:


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



Protein Sequence Analysis


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



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.


http://en.wikipedia.org/wiki/Structural_domain

http://en.wikipedia.org/wiki/Tertiary_structure

http://en.wikipedia.org/wiki/Biological_evolution

http://en.wikipedia.org/wiki/Protein_folding

http://en.wikipedia.org/wiki/EF-hand

http://en.wikipedia.org/wiki/Calmodulin


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.



Protein Structure

Primary

Secondary

Tertiary

Quarternary


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

Taken from wikipedia


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

Protein Structure


NCBI


Finding Protein Structure

PDB

Entrez Structure

NCBI BLINK via Entrez Gene/Protein



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..)


http://www.kosmix.com/topic/protein_data_bank?

http://www.rcsb.org/

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

http://molvis.sdsc.edu/fgij/whatis.htm


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)



Manipulating the Structure Viewer Window

Find Similar Structure: NCBI VAST



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.


http://www.ncbi.nlm.nih.gov/sutils/static/blinkhelp.html

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein


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


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


Hands-on Protein Structure of Chronophin





Sequence Alignment in Cn3D

NCBI


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.



Licensed Tools for Gene/Protein Information



HSLS Licensed Tools

BioBase Metacore Ingenuity IPA


Gene/Protein facts from Biobase


http://goo.gl/9wpwG


http://goo.gl/9wpwG

BioBase BioKnowledge Library



Protein Function from IPA



Thank you!Any questions?

Ansuman [email protected]




literature informatics august 20 , 2013

Documents

pubmed http

molecular biology http

university of pittsburgh

scientific papers http

medical university

appropriate literature

human genome project

university of nebraska