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Prediction of protein networks through data integration

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Lars Juhl Jensen
Lars Juhl Jensen

The document discusses methods for predicting protein-protein interaction networks through integrating diverse data sources. It describes the STRING database which predicts interactions between proteins in 373 genomes using genomic context methods, co-expression data, experiments, and literature mining. It also discusses NetworKIN, a method that predicts phosphorylation sites and potential kinase-substrate relationships through integrating phosphoproteomics data, sequence motifs, and network context. Benchmarking shows NetworKIN can predict interactions with over 2.5-fold greater accuracy compared to sequence-based methods alone by incorporating network context.

Technology
1 of 135
Prediction of protein networks through data integration Lars Juhl Jensen EMBL Heidelberg
prediction of interactions
STRING
 
functional interactions
373 genomes
model organism databases
Ensembl
Genome Reviews
RefSeq
genomic context methods
gene neighborhood
 
gene fusion
 
phylogenetic profiles
 
 
 
 
Cell Cellulosomes Cellulose
correct interactions
wrong associations
phylogenetic profiles
 
SVD Singular Value Decomposition
Euclidian distance
gene neighborhood
 
sum of intergenic distances
raw quality scores
rank by reliability
not comparable
Euclidian distance
sum of intergenic distances
benchmarking
calibrate vs. gold standard
 
raw quality scores
probabilistic scores
curated knowledge
many sources
KEGG Kyoto Encyclopedia of Genes and Genomes
Reactome
PID NCI-Nature Pathway Interaction Database
STKE Signal Transduction Knowledge Environment
MIPS Munich Information center for Protein Sequences
Gene Ontology
different gene identifiers
synonyms list
literature mining
M EDLINE
SGD Saccharomyces Genome Database
The Interactive Fly
OMIM Online Mendelian Inheritance in Man
co-mentioning
NLP Natural Language Processing
[object Object],[object Object],[object Object],[object Object],[object Object]
calibrate vs. gold standard
 
primary experimental data
gene expression
GEO Gene Expression Omnibus
expression compendia
protein interactions
BIND Biomolecular Interaction Network Database
BioGRID General Repository for Interaction Datasets
DIP Database of Interacting Proteins
IntAct
MINT Molecular Interactions Database
HPRD Human Protein Reference Database
many sources
different gene identifiers
redundancy
not comparable
merge data by publication
raw quality scores
calibrate vs. gold standard
 
combine all evidence
spread over many species
transfer by orthology
na ïve Bayesian scoring
 
prediction of interactions
NetworKIN
 
the idea
phosphoproteomics
mass spectrometry
 
phosphorylation sites
Phospho.ELM
in vivo
kinases are unknown
computational methods
NetPhosK
Scansite
sequence motifs
 
kinase families
overprediction
no context
what a kinase could do
not what it actually does
context
co-activators
scaffolders
protein networks
 
the algorithm
NetworKIN
 
benchmarking
Phospho.ELM
 
2.5-fold better accuracy
context is crucial
global statistics
 
visualization
 
ATM signaling
 
experimental validation
summary
reanalysis
benchmarking
integration
complementary data types
computational methods
reproduce what is know
biological discoveries
testable hypotheses
Acknowledgments ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

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