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Laboratory of Parasitic Diseases, NIAID MINING FOR MEANING: Data mining & Knowledge extraction Data interpretation Experiment Results Knowledge Conclusions Data interpretation Experiment Results Knowledge Conclusions High publication rates Data interpretation Experiment Results High-throughput screening Knowledge Conclusions High publication rates Data interpretation Experiment GENE EXPRESSION PROFILING Results Identify relevant genes Identify expression patterns Pathogens Bm 5 Mtb Bm 50 Ld DC Tg Lm Knowledge Induced by Fold Change (log2) 6 5 4 3 intracellular pathog 2 1 0 -1 -2 7 6 5 4 Leishmania & TB 3 2 1 0 -1 -2 7 Fold Change (log2) 6 5 4 3 2 Toxoplasma & TB 1 0 -1 -2 6 5 Fold Change (log2) Genes Conclusions Fold Change (log2) 9 8 4 3 2 1 0 -1 -2 Toxoplasma Data interpretation Experiment GENE EXPRESSION PROFILING Results Identify relevant genes Identify expression patterns Knowledge FUNCTIONAL PROFILING Identify functional implications Conclusions MINING FOR MEANING: FUNCTIONAL PROFILING IL-4 + GM-CSF DC Infection with 5 pathogens RNA pools -overnight- M-CSF Elutriated Human Monocytes U95 Mac 7 donors Intracellular Protozoan Toxoplasma gondii vs vs Bacteria Extracellular Brugia malayi Leishmania Mycobacterium tuberculosis Leishmania major vs Leishmania donovani Gene expression profiling DC Mac Dataset Dataset Extraction Filter 12.000 genes 1200 75 Bm 5 Mtb Bm 50 Tg Induced by 6 Fold Change (log2) Pathogens Ld Lm DC 5 4 3 2 intracellular pathogens 1 0 -1 -2 8 7 6 5 4 3 2 Leishmania & TB 1 0 -1 -2 Fold Change (log2) 7 6 5 4 3 2 Toxoplasma & TB 1 0 -1 -2 6 5 Fold Change (log2) Genes Fold Change (log2) 9 4 3 2 1 0 -1 -2 Toxoplasma MINING FOR MEANING: FUNCTIONAL PROFILING WITH GENE ONTOLOGIES - GO http://www.geneontology.org/ http://apps1.niaid.nih.gov/david/ MINING FOR MEANING: FUNCTIONAL PROFILING WITH GENE ONTOLOGIES - GO WITH LITERATURE ONTOLOGIES - MESH http://www.nlm.nih.gov/mesh/MBrowser.html http://array.ucsd.edu/hapi/ http://132.239.155.52/HAPI/TEST_377.HTML MINING FOR MEANING: FUNCTIONAL PROFILING WITH GENE ONTOLOGIES - GO WITH LITERATURE ONTOLOGIES - MESH WITH LITERATURE ABSTRACTS Data interpretation Experiment Results Knowledge Conclusions 12 million references Data interpretation Pathogens Bm 5 Mtb Bm 50 Ld DC Tg Lm Experiment Induced by Fold Change (log2) 6 5 4 3 intracellular patho 2 1 0 -1 -2 7 6 5 4 Leishmania & T 3 2 1 0 -1 -2 7 6 Fold Change (log2) Genes Results Fold Change (log2) 9 8 5 4 3 2 Toxoplasma & T 1 0 -1 -2 6 Fold Change (log2) 5 4 3 2 1 0 -1 -2 Knowledge Conclusions 12 million references Toxoplasma MINING FOR MEANING: FUNCTIONAL PROFILING WITH LITERATURE ABSTRACTS Co-citation Network http://www.pubgene.com/ MINING FOR MEANING: FUNCTIONAL PROFILING WITH LITERATURE ABSTRACTS Co-citation Network Natural Language Processing MINING FOR MEANING: FUNCTIONAL PROFILING WITH LITERATURE ABSTRACTS Co-citation Network Natural Language Processing Literature Profiling 1.Gene - Literature indexation Gene A Gene B Retrieve relevant literature C… for each gene Gene Gene X Abstracts 2. Analysis of abstract contents Gene A Gene B Gene C… Gene X Term1 0% 54% 2% Term 2 12% 0% 6% Term 3… 60% 1% 35% Term occurrences in abstracts Term y 2.5% 5% 7.5% 10% 12.5% 15% 17.5% 20% 22.5% 25% Determine term occurrence in abstracts Term occurrence in abstracts Chemokines Death / Apoptosis Analyze functional relationships Interferon response Dendrite elongation MHC class I pathway 3.Term filtering Select relevant Discrimination terms Co-occurrence - Identify functional relationships 1.Gene - Literature indexation Abstracts 2. Analysis of abstract contents Gene A Gene B Gene C… Gene X Term1 0% 54% 2% Term 2 12% 0% 6% Term 3… 60% 1% 35% Term occurrences in abstracts Term y 3.Term filtering 25% 20% 22.5% Select relevant 17.5% 12.5% 15% 7.5% 10% - Interpret data 5% Determine term occurrence in abstracts 2.5% - Translate genelists into keywords Gene A Gene B Retrieve relevant literature C… for each gene Gene Gene X Discrimination terms CoCo-occurrence Term occurrence in abstracts Chemokines Death / Apoptosis Analyze functional relationships Interferon response Dendrite elongation MHC class I pathway Pathogens Bm 5 Mtb Bm 50 Ld Tg Lm Experimental system DC Fold Change (log2) 5 4 3 intracellular pathogens 2 1 0 -1 -2 Fold Change (log2) 9 8 7 6 5 4 Leishmania & TB 3 2 Gene List 1 0 -1 -2 7 Fold Change (log2) 6 5 4 3 2 Toxoplasma & TB 1 0 -1 -2 6 5 Fold Change (log2) Genes KNOWLEDGE Induced by 6 4 3 2 1 0 -1 -2 Toxoplasma 12 million references MINING FOR MEANING: FUNCTIONAL PROFILING LITERATURE MINING Data interpretation Experiment Results Knowledge Conclusions High publication rates MINING FOR MEANING: DATA MINING LITERATURE MINING DOCUMENT CLUSTERING MINING FOR MEANING: DATA MINING LITERATURE MINING DOCUMENT CLUSTERING NLP MINING FOR MEANING: DATA MINING LITERATURE MINING DOCUMENT CLUSTERING NLP LITERATURE PROFILING Data interpretation Experiment GENE EXPRESSION PROFILING Results Identify relevant genes Identify expression patterns Pathogens Bm 5 Mtb Bm 50 Ld DC Tg Lm Knowledge Induced by Fold Change (log2) 6 5 4 3 intracellular pathog 2 1 0 -1 -2 7 6 5 4 Leishmania & TB 3 2 1 0 -1 -2 7 Fold Change (log2) 6 5 4 3 2 Toxoplasma & TB 1 0 -1 -2 6 5 Fold Change (log2) Genes Conclusions Fold Change (log2) 9 8 4 3 2 1 0 -1 -2 Toxoplasma