STRING/STITCH tutorial

Exploring proteins, chemicals and their

interactionswith STRING and STITCH

Michael Kuhn

(talk and practical session)

interactions of proteins and chemicals

example

Tryptophan synthase beta chainE. Coli K12

example

aspirinHomo sapiens

STRING: version 8.3soon: version 9

interactions of proteins

STITCH: version 2interactions of

proteins and chemicals

content

STRING 8

630 genomes

only completely sequenced genomes

STRING 9: >1100 genomes

2.5 million genes

(not proteins)

74,000 chemicals

(including 2200 drugs)

many sources of interactions

genomic context methods

gene neighborhood

gene fusion

phylogenetic profiles

curated knowledge

Texperimental evidence

GEO: Gene Expression Omnibus

co-expression

experimental databases

literature

variable quality

different “raw scores”

benchmarking

calibrate against “gold standard”(KEGG)

probabilistic scores

e.g. “70% chance for an association”

combine all evidence

Bayesian scoring scheme

e.g.: two scores of 0.7combined probability: ?

e.g.: two scores of 0.7combined probability: 0.91

1 - (1-0.7)2 = 0.91

evidence spread over many species

evidence transfer

transfer by orthology

(or “fuzzy orthology”)

von Mering et al., Nucleic Acids Research, 2005

von Mering et al., Nucleic Acids Research, 2005

two modes

proteins mode

von Mering et al., Nucleic Acids Research, 2005

maximum specificitylower coverage

information will be relevant for selected species

COG mode

“clusters of orthologous groups”

von Mering et al., Nucleic Acids Research, 2005

higher coveragelower specificity

includes all available evidence

some orthologous groups are too large to be meaningful

STRING plans

•next big release (9.0):

• coming end of 2010 / early 2011

• more genomes

• allow users to add more data to the network

STITCH plans

•next minor release (2.1):

• add ChEMBLdb

•next big release (3.0):

• “zoom” into stereo-isomers, salt forms

AcknowledgementsSTRINGChristian von MeringLars Juhl JensenManuel StarkSamuel ChaffronChris CreeveyJean MullerTobias DoerksPhilippe JulienAlexander RothMilan SimonovicPeer Bork

STITCHDamian SzklarczykAndrea FranceschiniMonica CampillosChristian von MeringLars Juhl JensenAndreas BeyerPeer Bork

string-db.orgJensen et al., NAR Database Issue 2009

stitch-db.orgKuhn et al., NAR Database Issue 2010