Cell Ontology – INCF Neuron Workshop

April 12-14, 2011Loudermilk Conference Center, Atlanta Georgia

Supported by NHGRI HG002273-09Zand

The International Neuroinformatics Coordinating Facility

Co-sponsored by the Georgia State University Center for Neuromics

Thanks to

• Janis Breeze, INCF• Jyl Boline, INCF• Paul Katz, GSU• Alan Ruttenburg, SUNY Buffalo• Judith Blake, The Jackson Laboratory• Ashley Stanton, The Jackson Laboratory• Beth Partridge, Hurley Travel at Jax

Participants

Workshop Goals

• Introduction to the Cell Ontology• Review of neuron ontology efforts• Discussion of the ontological representation

of neurons• Review of core set of high level neuron terms• Set up Working Groups• Working Groups develop neuron terms and

report back

Satellite Meeting

• For in depth discussion of ontology development-related issues

• Discussion points to be collects during main meeting

• For instance, “How do we present lines of evidence for asserted neuron properties as part of the ontology?”

The Cell Ontology• An ontology of cell types built by biologists for the needs of

data annotation and analysis.

• The Cell Ontology covers in vivo cell types from all of biology.

• The Cell Ontology is not– A list of specific cell lines, immortal or otherwise, although the Cell

Ontology may be used to describe such cells if they correspond to an in vivo cell type.

– A list of in vitro methods for preparing cell cultures, although the Cell Ontology may be used to describe the resulting cells if they correspond to an in vivo cell type.

OBO Reference Ontologies

RELATION TO TIME

GRANULARITY

CONTINUANT OCCURRENT

INDEPENDENT DEPENDENT

ORGAN ANDORGANISM

Organism(NCBI

Taxonomy?)

Anatomical Entity

(FMA, CARO)

OrganFunction

(FMP, CPRO) Phenotypic

Quality(PaTO)

Organism-Level Process

(GO)

CELL AND CELLULAR

COMPONENT

Cell(CL)

Cellular Compone

nt(FMA, GO)

Cellular Function

(GO)

Cellular Process

(GO)

MOLECULEMolecule

(ChEBI, SO,RnaO, PrO)

Molecular Function(GO)

Molecular Process

(GO)Smith et al., Nature Biotechnology 25, 1251 - 1255 (2007)

Overview of Cell Ontology• Developed by Jonathan Bard, David States,

Michael Ashburner, and Seung Rhee and first described in 2005, Genome Biology, 6:R21.

• The Cell Ontology is sometimes called the Cell Type Ontology, and often referred to as the “CL”, based on its identifier space. For instance the term “B cell” has the ID “CL:0000236”

• The CL currently has over 1500 cell type terms, over 500 of which have logical definitions.

Textual Definitions

• name: CD4-positive, CD25-positive, alpha-beta regulatory T cell

• def: "A CD4-positive, CD25-positive, alpha-beta T cell that regulates overall immune responses as well as the responses of other T cell subsets through direct cell-cell contact and cytokine release.”

• name: induced T-regulatory cell• def: "CD4-positive alpha-beta T cell

with the phenotype CD25-positive, CTLA-4-positive, and FoxP3-positive with regulatory function."

Logical Definitions

Logical Definitions

Pre-reasoning Post-reasoning

Logical Definitions of Neurons• Retinal Ganglion Cell

– def: "A neuron located in the ganglion cell layer of the eye that receives inputs via bipolar, horizontal and amacrine cells. The axons of these cells make up the optic nerve." [GOC:add, GOC:dph]

CL Neuron Improvements so far• We have added textual definitions for around

120 of the existing neuron types in CL, and logical definitions for around 75 of these.

• With help from INCF, we have imported 130 neuron types from the BAMS (Brain Architecture Management System) and created new genus-differentia textual definitions for these. About 40 of these have been given logical definitions.

• These changes are still under review.

Neurons are complicated• Most neurons are defined in part by their anatomical location.

– Brain and nervous system anatomy varies considerably between species.– Many anatomical systems exist for brains of different species. These are often in

conflict with each other.– Neurons often have their soma in one anatomical location, axon in another, and

dendrites in a third.

• We hope upper level neuron classes that can be defined reliably across species.

– Morphology– Neurotransmitter secretion– Large scale anatomical structures– Function

What does it mean to “represent” a Neuron in an Ontology?

• Capture basic properties of particular neurons in a textual definition based on the literature. The combination of properties should uniquely define the neuron.

• Translate these properties to a logical definition (cross-product), based on relations that link the neuron to terms in other ontologies.

• Not a mathematical model.

Neuron Ontology and Database Efforts

• Neurolex and NIF-cell• INCF Neuron Registry Task Force• Petilla Interneuron Nomenclature Group• SenseLab• NeuronBank• Brain Architecture Management System (BAMS)• Foundational Model of Anatomy• Virtual FlyBrain