Modeling of complex systems: what is relevant?

Modeling of complex systems:what is relevant?

Arno Knobbe, Marvin Meeng, Joost KokLeiden Institute of Advanced Computer Science (LIACS)

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

Role of LIACS in the modeling process

high-throughput datagenomics

transcriptomicsproteomics

metabolomics

important entitiesgenes

proteinsmetabolites

DataMining

DataMining

relevant conceptschromosomes

biological processespathways

transcription factorsdomain specific…

refined experimental setupselected genes

metabolitesexternal variables (O2, CO2, heat)

mathematical modelingdifferential equations

quantitative, timehigh resolution

Wikipathwaysliteraturedomain knowledge

Example: Understanding Neuroblastoma Genomic location

1. chromosome = 112. chromosome = X3. chr_arm = 11q4. chromosome = 17

GO-terms1. cell cycle2. Focal adhesion3. DNA replication4. Adherens junction

Protein families1. Cadherin_22. Cadherin3. Kinesin4. HEAT

Transcription factors1. NOVA2: Neuro-oncological

ventral antigen 2 2. Camta1: Calmodulin-

binding transcription activator 1 3. SELS Selenoprotein S

Pathways (Wikipathways)

Neoplastic processes1. Malignant Prolactinoma2. Anaplastic Oligoastrocytoma3. Adrenal neuroblastoma

Literature as Background Knowledge

concepts taken from Unified Medical Language System gene dictionary

MEDLINE abstracts Express detailed findings in terms of biological

vocabulary

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

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

Contact

dr. Arno Knobbewww.liacs.nl/~knobbeknobbe@liacs.nl

prof. dr. Joost Kokwww.liacs.nl/~joostjoost@liacs.nl