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Large-scale biomedical data and text integration

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Lars Juhl Jensen
Lars Juhl Jensen

Large-scale biomedical data and text integration

Sciences
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Protein association networks Lars Juhl Jensen
association networks
guilt by association
biological systems
molecular networks
STRING
2000+ genomes
computational predictions
gene fusion
Korbel et al., Nature Biotechnology, 2004
gene neighborhood
Korbel et al., Nature Biotechnology, 2004
phylogenetic profiles
Korbel et al., Nature Biotechnology, 2004
a real example
Cell Cellulosomes Cellulose
experimental data
gene coexpression
protein interactions
Jensen & Bork, Science, 2008
curated knowledge
complexes
pathways
Letunic & Bork, Trends in Biochemical Sciences, 2008
many databases
different formats
different identifiers
variable quality
not comparable
not same species
hard work
(Ph.D. students)
parsers
mapping files
common identifiers
clever ideas
quality assessment
scoring schemes
affinity purification
von Mering et al., Nucleic Acids Research, 2005
microarray experiments
Oliva et al., PLOS Biology, 2005
phylogenetic profiles
score calibration
gold standard
von Mering et al., Nucleic Acids Research, 2005
implicit weighting by quality
common scale
interologs
homology-based transfer
orthologous groups
Franceschini et al., Nucleic Acids Research, 2013
missing most of the data
Biomedical text mining Lars Juhl Jensen
>10 km
too much to read
exponential growth
~40 seconds per paper
computer
as smart as a dog
teach it specific tricks
named entity recognition
comprehensive lexicon
CDC2
cyclin dependent kinase 1
orthographic variation
expansion rules
prefixes and suffixes
CDC2
hCdc2
flexible matching
spaces and hyphens
cyclin dependent kinase 1
cyclin-dependent kinase 1
“black list”
SDS
information extraction
co-mentioning
counting
within documents
within paragraphs
within sentences
scoring scheme
score calibration
natural language processing
grammatical analysis
part-of-speech tagging
what you learned in school pronoun pronoun verb preposition noun
multiword detection
compound nouns in Danish
semantic tagging
words of special interest
sentence parsing
Gene and protein names Cue words for entity recognition Verbs for relation extraction [nxexpr The expression of [nxgene the cytochrome genes [nxpg CYC1 and CYC7]]] is controlled by [nxpg HAP1]
text corpus
~22 million abstracts
Medline
~2 million full-text articles
restricted access
Mini exercise 1 Go to http://string-db.org Query for Mt H37Rv adhD (Rv3086) Change between different views Check evidence for adhD–lipR
Mini exercise 2 Go to the paper PMC2995261 Extract the protein names in table 1 Create STRING network of them Change to “advanced” mode
multi-page tables
Large-scale data integration Lars Juhl Jensen
general approach
curated knowledge
experimental data
text mining
computational predictions
common identifiers
quality scores
score calibration
visualization
STRING
protein networks
string-db.org
STITCH
chemical networks
stitch-db.org
PubChem
metabolic pathway maps
drug target databases
high-throughput screening
COMPARTMENTS
subcellular localization
compartments.jensenlab.org
Gene Ontology
GO annotations
UniProtKB
model organism databases
sequence-based predictions
PSORT
YLoc
TISSUES
tissue expression
tissues.jensenlab.org
Brenda Tissue Ontology
high-throughput studies
EST libraries
microarrays
RNA-Seq
mass spectrometry
immunohistochemistry
DISEASES
disease associations
text mining
genetics databases
Genetics Home Reference
GWAS studies
NHGRI GWAS Catalog
cancer mutation data
COSMIC
Work on your own data string-db.org stitch-db.org compartments.jensenlab.org tissues.jensenlab.org diseases.jensenlab.org
Medical text data mining Lars Juhl Jensen
structured data
Jensen et al., Nature Reviews Genetics, 2012
unstructured data
central registries
individual hospitals
opt-out
opt-in
Danish registries
civil registration system
CPR number
established in 1968
Jensen et al., Nature Reviews Genetics, 2012
national discharge registry
14 years
6.2 million patients
45 million admissions
68 million records
119 million diagnosis
ICD-10
Jensen et al., Nature Reviews Genetics, 2012
not research
reimbursement
diagnosis trajectories
naïve approach
comorbidity
Jensen et al., Nature Reviews Genetics, 2012
confounding factors
“known knowns”
gender
age
type of hospital encounter
Jensen et al., Nature Communications, 2014
“known unknowns”
smoking
diet
“unknown unknowns”
reporting biases
matched controls
temporal correlations
multiple testing
trajectories
Jensen et al., Nature Communications, 2014
trajectory networks
Jensen et al., Nature Communications, 2014
key diagnoses
Jensen et al., Nature Communications, 2014
direct medical implications
electronic health records
structured data
Jensen et al., Nature Reviews Genetics, 2012
unstructured data
free text
Danish
busy doctors
typos
psychiatric patients
custom dictionaries
diseases
drugs
adverse drug reactions
expansion rules
Clozapine
Clozapine clozapi n clossapi n klozapin e chlosapi n chlozapi chlosapi ne n chlozapi ne klossapi n closapin e klozapi klosapi n n
post-coordination rules
failure of kidney
kidney failure
pharmacovigilance
clinical trials
spontaneous reports
underreporting
data mining
structured data
medication
semi-structured data
drug indications
known ADRs
unstructured data
adverse drug reactions
temporal correlations
hand-crafted rules
Drug introduction Adverse event Drug discontinuation Negative modifier Indication Pre-existing Adverse event Eriksson et al., Drug Safety, 2014 condition Adverse drug reaction Possible adverse drug reaction ADR of additional drug
Drug introduction Identification star t Adverse event Drug discontinuation Negative modifier Indication Pre-existing Adverse event Eriksson et al., Drug Safety, 2014 condition Adverse drug reaction Possible adverse drug reaction ADR of additional drug
Drug introduction Drug discontinuation Negative modifier Indication Pre-existing Adverse event Eriksson et al., Drug Safety, 2014 condition Adverse drug reaction Possible adverse drug reaction Adverse event ADR of additional drug Identification star t
Drug introduction Drug discontinuation Negative modifier Indication Pre-existing Adverse event Eriksson et al., Drug Safety, 2014 condition Adverse drug reaction Possible adverse drug reaction Adverse event ADR of additional drug Identification star t
recall known ADRs
estimate ADR frequencies
Eriksson et al., Drug Safety, 2014
discover new ADRs
Drug substance ADE p-value Chlordiazepoxide Nystagmus 4.0e-8 Simvastatin Personality changes 8.4e-8 Dipyridamole Visual impairment 4.4e-4 Citalopram Psychosis 8.8e-4 Bendroflumethiazi Apoplexy 8.5e-3 de Eriksson et al., Drug Safety, 2014
Acknowledgments Molecular networks Christian von Mering Damian Szklarczyk Michael Kuhn Manuel Stark Samuel Chaffron Chris Creevey Jean Muller Tobias Doerks Philippe Julien Alexander Roth Milan Simonovic Jan Korbel Berend Snel Martijn Huynen Peer Bork Localization and disease Sune Frankild Jasmin Saric Evangelos Pafilis Kalliopi Tsafou Alberto Santos Janos Binder Heiko Horn Michael Kuhn Nigel Brown Reinhardt Schneider Sean O’ Donoghue Medical data mining Anders Boeck Jensen Peter Bjødstrup Jensen Robert Eriksson Francisco S. Roque Henriette Schmock Marlene Dalgaard Massimo Andreatta Thomas Hansen Karen Søeby Søren Bredkjær Anders Juul Tudor Oprea Pope Moseley Thomas Werge Søren Brunak

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