large-scale biomedical data and text integration
DESCRIPTION
Large-scale biomedical data and text integrationTRANSCRIPT
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Protein association networks
Lars Juhl Jensen
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association networks
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guilt by association
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biological systems
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molecular networks
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STRING
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2000+ genomes
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computational predictions
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gene fusion
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Korbel et al., Nature Biotechnology, 2004
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gene neighborhood
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Korbel et al., Nature Biotechnology, 2004
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phylogenetic profiles
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Korbel et al., Nature Biotechnology, 2004
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a real example
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Cell
Cellulosomes
Cellulose
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experimental data
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gene coexpression
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protein interactions
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Jensen & Bork, Science, 2008
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curated knowledge
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complexes
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pathways
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Letunic & Bork, Trends in Biochemical Sciences, 2008
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many databases
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different formats
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different identifiers
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variable quality
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not comparable
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not same species
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hard work
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(Ph.D. students)
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parsers
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mapping files
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common identifiers
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clever ideas
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quality assessment
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scoring schemes
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affinity purification
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von Mering et al., Nucleic Acids Research, 2005
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microarray experiments
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Oliva et al., PLOS Biology, 2005
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phylogenetic profiles
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score calibration
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gold standard
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von Mering et al., Nucleic Acids Research, 2005
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implicit weighting by quality
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common scale
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interologs
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homology-based transfer
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orthologous groups
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Franceschini et al., Nucleic Acids Research, 2013
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missing most of the data
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Lars Juhl Jensen
Biomedical text mining
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>10 km
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too much to read
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exponential growth
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~40 seconds per paper
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computer
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as smart as a dog
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teach it specific tricks
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named entity recognition
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comprehensive lexicon
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CDC2
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cyclin dependent kinase 1
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orthographic variation
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expansion rules
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prefixes and suffixes
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CDC2
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hCdc2
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flexible matching
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spaces and hyphens
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cyclin dependent kinase 1
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cyclin-dependent kinase 1
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“black list”
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SDS
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information extraction
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co-mentioning
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counting
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within documents
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within paragraphs
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within sentences
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scoring scheme
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score calibration
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natural language processing
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grammatical analysis
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part-of-speech tagging
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what you learned in schoolpronoun pronoun verb preposition noun
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multiword detection
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compound nouns in Danish
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semantic tagging
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words of special interest
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sentence parsing
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Gene and protein namesCue words for entity recognitionVerbs for relation extraction
[nxexpr The expression of [nxgene the cytochrome genes [nxpg CYC1 and CYC7]]]is controlled by[nxpg HAP1]
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text corpus
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~22 million abstracts
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Medline
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~2 million full-text articles
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restricted access
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Mini exercise 1Go to http://string-db.org
Query for Mt H37Rv adhD
(Rv3086)
Change between different
views
Check evidence for adhD–lipR
link
Extent network to 50
interactors
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Mini exercise 2Go to the paper PMC2995261
Extract the protein names in
table 1
Create STRING network of
them
Change to “advanced” mode
Analyze for clusters and
enrichment
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multi-page tables
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Large-scale data integration
Lars Juhl Jensen
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general approach
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curated knowledge
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experimental data
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text mining
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computational predictions
![Page 122: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/122.jpg)
common identifiers
![Page 123: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/123.jpg)
quality scores
![Page 124: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/124.jpg)
score calibration
![Page 125: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/125.jpg)
visualization
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STRING
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protein networks
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string-db.org
![Page 129: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/129.jpg)
STITCH
![Page 130: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/130.jpg)
chemical networks
![Page 131: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/131.jpg)
stitch-db.org
![Page 132: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/132.jpg)
PubChem
![Page 133: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/133.jpg)
metabolic pathway maps
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drug target databases
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high-throughput screening
![Page 136: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/136.jpg)
COMPARTMENTS
![Page 137: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/137.jpg)
subcellular localization
![Page 138: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/138.jpg)
compartments.jensenlab.org
![Page 139: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/139.jpg)
Gene Ontology
![Page 140: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/140.jpg)
GO annotations
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UniProtKB
![Page 142: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/142.jpg)
model organism databases
![Page 143: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/143.jpg)
sequence-based predictions
![Page 144: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/144.jpg)
PSORT
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YLoc
![Page 146: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/146.jpg)
TISSUES
![Page 147: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/147.jpg)
tissue expression
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tissues.jensenlab.org
![Page 149: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/149.jpg)
Brenda Tissue Ontology
![Page 150: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/150.jpg)
high-throughput studies
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EST libraries
![Page 152: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/152.jpg)
microarrays
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RNA-Seq
![Page 154: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/154.jpg)
mass spectrometry
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immunohistochemistry
![Page 156: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/156.jpg)
DISEASES
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disease associations
![Page 158: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/158.jpg)
text mining
![Page 159: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/159.jpg)
genetics databases
![Page 160: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/160.jpg)
Genetics Home Reference
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GWAS studies
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NHGRI GWAS Catalog
![Page 163: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/163.jpg)
cancer mutation data
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COSMIC
![Page 165: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/165.jpg)
Work on your own datastring-db.org
stitch-db.org
compartments.jensenlab.org
tissues.jensenlab.org
diseases.jensenlab.org
![Page 166: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/166.jpg)
Lars Juhl Jensen
Medical text data mining
![Page 167: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/167.jpg)
structured data
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Jensen et al., Nature Reviews Genetics, 2012
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unstructured data
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![Page 171: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/171.jpg)
central registries
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individual hospitals
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![Page 174: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/174.jpg)
opt-out
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opt-in
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Danish registries
![Page 177: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/177.jpg)
civil registration system
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CPR number
![Page 179: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/179.jpg)
established in 1968
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Jensen et al., Nature Reviews Genetics, 2012
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national discharge registry
![Page 182: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/182.jpg)
14 years
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6.2 million patients
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45 million admissions
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68 million records
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119 million diagnosis
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ICD-10
![Page 188: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/188.jpg)
Jensen et al., Nature Reviews Genetics, 2012
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not research
![Page 190: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/190.jpg)
reimbursement
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diagnosis trajectories
![Page 192: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/192.jpg)
naïve approach
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comorbidity
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Jensen et al., Nature Reviews Genetics, 2012
![Page 195: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/195.jpg)
confounding factors
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“known knowns”
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gender
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age
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type of hospital encounter
![Page 200: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/200.jpg)
Jensen et al., Nature Communications, 2014
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“known unknowns”
![Page 202: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/202.jpg)
smoking
![Page 203: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/203.jpg)
diet
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“unknown unknowns”
![Page 205: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/205.jpg)
reporting biases
![Page 206: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/206.jpg)
matched controls
![Page 207: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/207.jpg)
temporal correlations
![Page 208: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/208.jpg)
multiple testing
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trajectories
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Jensen et al., Nature Communications, 2014
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trajectory networks
![Page 212: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/212.jpg)
Jensen et al., Nature Communications, 2014
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key diagnoses
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Jensen et al., Nature Communications, 2014
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direct medical implications
![Page 216: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/216.jpg)
electronic health records
![Page 217: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/217.jpg)
structured data
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Jensen et al., Nature Reviews Genetics, 2012
![Page 219: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/219.jpg)
unstructured data
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![Page 221: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/221.jpg)
free text
![Page 222: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/222.jpg)
Danish
![Page 223: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/223.jpg)
busy doctors
![Page 224: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/224.jpg)
typos
![Page 225: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/225.jpg)
psychiatric patients
![Page 226: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/226.jpg)
custom dictionaries
![Page 227: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/227.jpg)
diseases
![Page 228: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/228.jpg)
drugs
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adverse drug reactions
![Page 230: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/230.jpg)
expansion rules
![Page 231: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/231.jpg)
Clozapine
![Page 232: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/232.jpg)
Clozapineclozapi
n
clossapin
klozapine
chlosapin
chlosapine
chlozapin
chlozapine
klossapin
closapine
klozapinklosapi
n
![Page 233: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/233.jpg)
post-coordination rules
![Page 234: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/234.jpg)
failure of kidney
![Page 235: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/235.jpg)
kidney failure
![Page 236: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/236.jpg)
pharmacovigilance
![Page 237: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/237.jpg)
clinical trials
![Page 238: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/238.jpg)
spontaneous reports
![Page 239: Large-scale biomedical data and text integration](https://reader030.vdocuments.mx/reader030/viewer/2022020718/558e70e51a28ab66638b468a/html5/thumbnails/239.jpg)
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underreporting
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data mining
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structured data
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medication
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semi-structured data
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drug indications
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known ADRs
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unstructured data
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adverse drug reactions
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temporal correlations
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hand-crafted rules
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Eriksson et al., Drug Safety, 2014
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Eriksson et al., Drug Safety, 2014
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Eriksson et al., Drug Safety, 2014
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Eriksson et al., Drug Safety, 2014
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recall known ADRs
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estimate ADR frequencies
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Eriksson et al., Drug Safety, 2014
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discover new ADRs
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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
Bendroflumethiazide
Apoplexy 8.5e-3
Eriksson et al., Drug Safety, 2014
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AcknowledgmentsMolecular networksChristian von MeringDamian SzklarczykMichael KuhnManuel StarkSamuel ChaffronChris CreeveyJean MullerTobias DoerksPhilippe JulienAlexander RothMilan SimonovicJan KorbelBerend SnelMartijn HuynenPeer Bork
Localization and diseaseSune FrankildJasmin SaricEvangelos PafilisKalliopi TsafouAlberto SantosJanos BinderHeiko HornMichael KuhnNigel BrownReinhardt SchneiderSean O’ Donoghue
Medical data miningAnders Boeck JensenPeter Bjødstrup JensenRobert ErikssonFrancisco S. RoqueHenriette SchmockMarlene DalgaardMassimo AndreattaThomas HansenKaren SøebySøren BredkjærAnders JuulTudor OpreaPope MoseleyThomas WergeSøren Brunak