1. Modeling of complex systems: what is relevant? Arno Knobbe, Marvin Meeng, Joost Kok Leiden Institute of Advanced Computer Science (LIACS)

2. Knowledge mining  Knowledge mining: Producing high-level insight by mining primary results in the context of existing knowledge.  Integration of detailed findings with (publicly available) domain knowledge  Knowledge sources  annotations: GO, KEGG, …  basic details: genomic location, …  interaction networks  detailed pathways: Wikipathways  literature: MEDLINE

3. Role of LIACS in the modeling process high-throughput data genomics transcriptomics proteomics metabolomics important entities genes proteins metabolites Data Mining Data Mining relevant concepts chromosomes biological processes pathways transcription factors domain specific… refined experimental setup selected genes metabolites external variables (O 2, CO 2, heat) mathematical modeling differential equations quantitative, time high resolution Wikipathways literaturedomain knowledge

4. Example: Understanding Neuroblastoma  Genomic location 1. chromosome = 11 2. chromosome = X 3. chr_arm = 11q 4. chromosome = 17  GO-terms 1. cell cycle 2. Focal adhesion 3. DNA replication 4. Adherens junction  Protein families 1. Cadherin_2 2. Cadherin 3. Kinesin 4. HEAT  Transcription factors 1. NOVA2: Neuro-oncological ventral antigen 2 2. Camta1:Calmodulin-binding transcription activator 1 3. SELSSelenoprotein S  Pathways (Wikipathways)  Neoplastic processes 1. Malignant Prolactinoma 2. Anaplastic Oligoastrocytoma 3. Adrenal neuroblastoma

5. Literature as Background Knowledge  concepts taken from  Unified Medical Language System  gene dictionary  MEDLINE abstracts  Express detailed findings in terms of biological vocabulary

6. Literature as Background Knowledge  Biological process (4825)  Molecular function (3370)  Cellular component (1613)  Cell (1197)  Tissue (736)  Gene to gene associations (24217 other genes)  Disorder (26410)  Neoplastic process (4307)  Pathological function (1912)  … as GO, but not annotations

7. Tracking concepts over time  Which concepts are relevant at each timepoint?  Track (multiple) winners through time  Metabolic Syndrome, genes involved in fatty diet:

8. Contact dr. Arno Knobbe www.liacs.nl/~knobbe knobbe@liacs.nl prof. dr. Joost Kok www.liacs.nl/~joost joost@liacs.nl