An Advanced Strategy for Integration of Biological Measurement Data Hiroshi Masuya 1, Georgios V. Gkoutos 2, Nobuhiko Tanaka 1, Kazunori Waki 1, Yoshihiro Okuda 3, Tatsuya Kushida 3, Norio Kobayashi 4, Koji Doi 4, Kouji Kozaki 5, Robert Hoehndorf 1, Shigeharu Wakana 1, Tetsuro Toyoda 4 and Riichiro Mizoguchi 5 ICBO 2011 July 28-30, 2011 Buffalo, New York, 1: RIKEN BioResource Center, Tsukuba, Japan 2: Department of Genetics, University of Cambridge, UK 3: NalaPro Technologies, Inc, Tokyo, Japan 4: RIKEN BASE, Yokohama Japan 5: Department of Knowledge Systems, ISIR, Osaka University, Japan

Motivation of this study Organism A Organism B Organism C Organism D Phenotypes represent a broad range of variations in measured qualities To contribute to development of the informatics infrastructure for the description, exchange and mining of phenotypic data. Integrated phenotypic information whole Sophisticated informatics infrastructure (ontology) Sophisticated informatics infrastructure (ontology) Biological knowledge Mining…

Phenotypic Quality (PATO): PATO provides a practical basis for vocabulary and semantics for the description of phenotype information across species. Single hierarchy model of “quality” suite for BFO Less confusions than “EAV” annotation for non-ontology-familiar people. HP: ! Amyotrophy PATO: ! atrophied FMA:30316 ! muscle MA: ! muscle PATO: ! atrophied MP: ! muscular atrophy Basis of inferences of cross-species phenotype equivalence with EQ. (e.g. mouse phenotype and disease) Standard of phenotype annotation across species. (“EQ” annotation) E Q E Q

Expansion of PATO We attempted to expand the PATO ontology to ensure a more advanced, explicit and consistent knowledge framework. 1.To provide fundamental classification of quality values on the basis of measurement scales. 2.To provide strict data model to operate context- dependencies of ordinal values. 3.To provide model of datum (or description) as a informational entity with the structure of common formalisms. Objectives:

Refrain from 2-hiearchy model (and EAV formalism) Refrain from 2-hiearchy model (and EAV formalism) There were a lot of discussions for PATO to take 1-hiearchy and EQ… Fundamental classification of quality-value (1) lengthtemperaturecolor 20cm 37 ℃ K Long, shorthigh, low red, blue.. This classification takes as starting point the mathematical operation! 1.Number of studies claims that the fundamental classification of values: “scales of measurement” (Stevens S.S, 1946) is beneficial for data integration in the field of experimental science.

2.Foundation of explicit description of change of quality is needed Growing boy and his height quality OntologySystem of quality Formalism BFO, PATO 1-hiearchyEQ DOLCE2-hiearchyEAV Qualitative and quantitative descriptions are integrated in a single knowledge framework in DOLCE. For the coordination of ongoing efforts, equivalence mapping of these systems is beneficial. Fundamental classification of quality-value (2) t1 t Explicit description of color change is needed. Color 1: green to orange Color 2: orange to green

“Small” class “Large” class I’m big!! I’m small.. Problem of “large ant and small elephant” value A value B value C value D How to classify value instances? Context A: simple comparison Threshold X (some value) larger smaller Model of context-dependency of ordinal value (1)

“abnormally large” class “abnormally small” class “normal size” class I’m big!! I’m small.. value A value C value B value D Context B: deviation based comparison (context of inference of cross-species equivalence of phenotypes) larger smaller larger smaller Threshold Y1 and Y2 (deviation-based value) deviation Model of context-dependency of ordinal value (2) Problem of “large ant and small elephant” How to classify value instances? Knowledge model of context dependencies of ordinal scale values is needed!

1.Distinction of a “true value” and an “empirical measurement” as an approximation is needed. 2.Modeling of informational entities with common formalisms (eg. EQ, EAV and so on) and their relationships would be useful! weigh t EQ EAV weigh t Model of datum as an informational entity Reality Information Current version of DOLCE, BFO and PATO deal only with the primary reality and do not deal with quality description. (Unknown…) (Unknown...) Current version of

A reference ontology “PATO2YAMATO” Expansion of PATO with YAMATO framework Features: Framework of interoperability of quality-related concepts between top-level ontologies. Support of classification of scales of measurements. Model of context dependency with “role” Detailed model of “representation” (an informational object) that involves quality representation. Yet Another More Advanced Top-Level Ontology (YAMATO: Mizoguchi, 2009) BFOYAMATO DOLCE PATO quality quale quality-space Practical use based proposals… Equivalence mapping between 1- and 2-hiearcy models Model of context dependency Model of datum with common formalisms OBI Mapping Interoperability

region quale quality space quality_ quantity quality value quality property quality BFO YAMATO DOLCE (Upper level) generic quality (convertible) (Upper level) Equivalence mapping of 1- and 2-hearcy model identical Classification of quality value (scales of measurements : Stevens S.S, 1946) About 1,000 PATO terms were manually mapped to YAMATO framework.

Modeling of context dependency with “role” An entity often plays different “roles” with different characteristics under different contexts (at school) (at home) Abnormally heavy large-role weight quality value Distribution for weight role-holder （ Entity playing a role) role potential player context heavier than normal value qualitative value for weight depend on playable In the distribution for weight, some weight quality values playing large-roles thereby becomes role holders, abnormally heavy Concept model of role and role-holder I’m a teacher.I’m a husband

Modeling of context dependency with “role” (at school) (at home) In the distribution for weight, some weight quality values playing large-roles thereby becomes role holders, abnormally heavy I’m a teacher.I’m a husband An entity often plays different “roles” with different characteristics under different contexts Implementation and representation in Hozo ontology editor context Role-holder player Potential

Inter-relationships among contexts Classification of organisms Inherit Inference of the Classification of “abnormally heavy” ”Abnormally light in elephant is lighter than abnormally heavy in ant” in the simple comparison context. Inference of classification:

Context of distribution of weight in elephant Context of distribution of weight in ant Simple comparison context Coordination of ordinary values under different contexts Abnormally heavy in elephant Normal weight in elephant Abnormally light in elephant Abnormally heavy in ant Normal weight in ant Abnormally light in ant larger

Quality representation in YAMATO Quality Weight Reality (Symbolization) Quality representation Informational entities YAMATO provides “quality representation” for the foundation of formalized informational entities such as EQ, EAV and so on. Basic structure for representation by symbol EP (=EQ) (BFO, PATO) EAV (DOLCE) Sentence of natural language Coding of genetic information TuppleTriplenatural languagenucleotide sequence *entity, #property*entity, #generic quality, value alphabetmolecular symbol quality measurement anything…Specification of gene product Quality representation is modeled in the consistent way for content bearing informational entity, “representation”. quality representation *: symbolization operation, #: Class => individual operation (equivalent with punning in OWL 2) (Mizoguchi, 2004)

Current status of the reference ontology: PATO2YAMATO 1,450 EQ annotation: ( OBO cross-product file for Mammalian Phenotype ontology ) EAV-quality representations in YAMATO framework reference: PATO2YAMATO Including about 1,000 PATO terms into YAMATO framework Basic form of context-dependent ordinal values are defined. They are workable under the classification of organisms. Basic form of quality representation (EAV and EQ) are already defined in YAMATO. Preliminary trial of simple conversion of EQ to EAV The ontology helps the automatic conversion from EQ to EAV! We are planning full conversion of EQ across multiple species with coordinated EAV- quality representation.

This study shows: YAMATO’s framework helps to coordinate different “qualities” for phenotype information in both of reality and description level. Role-model successfully coordinated ordinal values dependent on multiple contexts (deviation-based and simple comparison). Future views: Automatic conversion of EQ of multiple species to EAV. Modeling of contexts of experimental conditions. Integration of qualitative and quantitative phenotype data. Coordination of more complicated phenotype data sets from multiple species and experiments. Summary of this talk

RIKEN BioResource Center Nobuhiko Tanaka, Kazunori Waki, Terue Takatsuki University of Cambridge Georgios V. Gkoutos, Robert Hoehndorf NalaPro Technologies Inc Yoshihiro Okuda, Tatsuya Kushida Enegate corp Mamoru Ota RIKEN BASE Norio Kobayashi, Koji Doi, Tetsuro Toyoda Department of Knowledge Systems, ISIR, Osaka University Koji Kozaki, Riichiro mizoguchi Acknowledgements

貴為和以 “Harmony is to be valued.” In “Seventeen-article constitution” (A.D 603, YAMATO imperial court in ancient Japan) Authored by Prince Sh ō toku (A.D. 573–621) Thank you !