An Advanced Strategy for Integration of Biological Measurement Data

Hiroshi Masuya1, Georgios V. Gkoutos2, Nobuhiko Tanaka1, Kazunori Waki1, Yoshihiro Okuda3,

Tatsuya Kushida3, Norio Kobayashi4, Koji Doi4, Kouji Kozaki5, Robert Hoehndorf1,

Shigeharu Wakana1, Tetsuro Toyoda4 and Riichiro Mizoguchi5

ICBO 2011July 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, Japan4: 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:0003202 ! AmyotrophyHP:0003202 ! AmyotrophyPATO:0001623 !

atrophiedPATO:0001623 !

atrophied

FMA:30316 ! muscle

FMA:30316 ! muscle

MA:0000015 ! muscle

MA:0000015 ! muscle

PATO:0001623 ! atrophied

PATO:0001623 ! atrophied

MP:0002269 ! muscular atrophy

MP:0002269 ! 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)

length temperature color

20cm 37℃

- 310.15K

Long, short high, 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

Ontology System of quality

Formalism

BFO, PATO

1-hiearchy EQ

DOLCE 2-hiearchy EAV

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

t21 2

1 2

Explicit description of color change is needed.

Color 1: green to orangeColor 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) largersmaller

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!

weight

weight

weight

weight EQ

EAV

weight

weight

Model of datum as an informational entity

Reality

Reality

Information

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)

BFO YAMATO DOLCE

PATO

quality

qualequality-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)

(Upper level)

Equivalence mapping of 1- and 2-hearcy model

identical

identical

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)

Abnormallyheavy

large-roleweight

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 husbandAn entity often plays different “roles” with

different characteristics under different contexts

Implementation and representation in Hozo ontology editor

context

Role-holder

playerPotential

Inter-relationships among contexts

Classification of organisms

InheritInherit

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

larger

larger

larger

larger

Quality representation in YAMATO

Quality

Weight

Reality

(Symbolization)

Qualityrepresentation

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

Tupple Triple natural language nucleotide sequence

*entity, #property

*entity, #generic quality, value

alphabet molecular symbol

quality measurement

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.

http://www.brc.riken.go.jp/lab/bpmp/ontology/ontology_pato2yato.html

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 Shōtoku (A.D. 573–621)

Thank you !