Alzforum / Protein Ontology Kick-Off Meeting

The Alzforum / Protein Ontology collaboration is a driving biological project of the NIGMS-funded Protein Ontology initiative.

Goals of the meeting

The goal of this meeting is to initiate a project to create a protein information resource that will address the needs of Alzheimer's Disease (AD) researchers in a maximally effective way. The focus of the meeting will be directed primarily towards identifying these needs through discussion with specialists in different aspects of AD research. The intended long-term outcome will take the form of elaborations and extensions of the Protein Ontology (PRO), of new applications of the ontology to annotation of AD research results, and of new PRO-based software tools to support AD research.

Date and Venue

October 4-5, 2011, Hotel Indigo, Buffalo, NY

Topics to be addressed

Protein Variants

How can we most effectively represent information pertaining to the variants associated with AD and to the relations between them; for example, what level of specificity of descriptions of variants would best address the requirements of AD researchers? In the case of APP, for example, what are the genetic variants of relevance to APP? How should the Protein Ontology deal with such variants in order to assist researchers?

Aggregates of proteins / Protein complexes

What are the different kinds of aggregates and complexes relevant to AD, how do AD researchers treat them?

We envisage two case studies in the course of the meeting, both of which will be designed to serve as guidance for Protein Ontology developers in the initial phases of the project:

1. Protein case study: Perform a detailed review of one class of proteins important to AD research, chosen to be part of the research agenda of at least one of the AD scientists, to bring all participants up to the same level of understanding about what is known. Issues to be addressed will include:

importance of recording non-protein constituents

multimerism

relations to disease hypotheses

kinds of evidence

research plan

protein knowledge queries that would aid the AD researchers

protein knowledge queries that would help others retrieve AD research results

2. Protein complex case study: In addition to the issues addressed above as these arise for protein complexes, this case study will address in addition: criteria for being a complex - what amount of stability is necessary, component stoichiometry and structure, modifications/changes to complexes and associated functional changes.

Schedule

Monday, October 3

From 7:00pm Dinner / Informal Reception, Blue Fire Restaurant, Marriott Hotel (next door to Indigo Hotel)

Tuesday, October 4

8:30am Continental Breakfast

9:30am Moderator: Darren Natale

• Alan Ruttenberg: Introduction to the Project
• Dominic Walsh: Introduction to Alzheimer's Disease Research
• Barry Smith: Introduction to Ontology for Biomedical Scientists
• Cathy Wu: Introduction to the Protein Ontology

10:30am Refreshment Break

11:00am

• Elizabeth Wu: The Alzforum

12:30pm Lunch

1:30pm Moderator: Barry Smith

• Cecilia Arighi: Short Tutorial on the PRO Website and Associated Tools

3:00pm Refreshment Break

3:30 Moderator: Darren Natale

• Michael Wolfe: The Amyloid Hypothesis of Alzheimer Pathogenesis
• Tim Danford: On Using Exons to Define Isoforms

6:00pm Dinner: 270 Campbell Blvd, Getzville, NY 14068.

Wednesday, October 5

8:30am Continental Breakfast

9:00am Moderator: Cathy Wu Review of Existing Coverage of AD-Related Proteins

• Peter d'Eustachio: Reactome

• Darren Natale: PRO Coverage of AD-Related Proteins

• Fahim Imam: Neuroscience Information Framework (NIF) and the Neurodegenerative Disease Phenotype Ontology

• Paolo Ciccarese: Annotation of Neuroscientific Data

AlzSwan Example

10:30am Refreshment Break

11:00am *Alex Diehl: Neurological Disease Ontology

11:45 Discussion of sample research questions

• Find all Creb1 isoform(s) expresssed in the brain by cell type and the antibodies that can be used to detect them
• What is the relationship of obesity and type I and II diabetes to AD?
• What is the expression of AD-related genes in obesity and diabetes?
• What is the effect of insulin on pathology, clinical manifestations and neuroimaging in AD?
• What is the effect of insulin in expression of AD-related genes?
• What is APP695?
• What are the recorded phosphorylation sites in human APP?
• What are the recorded substrates of gamma secretase in human cells?
• What proteins interact with APP?
• What are the transcriptional targets of AICD?
• Which antibodies target the C terminus of human APP?
• Which cleavage products of APP are secreted?
• What forms of Abeta have been found in human brain (vs. in cell culture, mouse brain, etc.)?
• How does Abeta affect mitochondria?
• Which kinases phosphorylate Tau at threonine 181?
• What are the defined domains in human APP? How do these domains compare to those in mouse?
• What Abeta peptides longer than 43 amino acids (starting at Asp-1) are found in amyloid plaques?
• Wild type 3RTau found as predominant species of Tau in neurofibrillar tangles in certain disease states.

12:30pm Lunch

1:30pm Case Studies

• Expert review of PRO definitions

Tau

Amyloid beta

Potential additional topics for discussion

• Animal Models
• Alzheimer's Disease according to KEGG

2:30pm Project planning

• Three possible uses for a resource like PRO in a field such as AD research:

To enable more powerful computation in information-driven research

To aid non-experts in a given field to access information in that field

To aid experts in the field find new information, identify new hypothesis, or perform virtual testing of existing hypotheses

• Delineating the biological systems relevant to AD

3:30pm Main meeting ends / Refreshment Break

Technical session for selected participants during rest of day.

• Coordination of Alzforum and PRO Curation

6:00pm Dinner

Participants

• Cecilia Arighi (PRO / University of Delaware)
• Paolo Ciccarese (Massachusetts General Hospital / Harvard Medical School, Boston)
• Alexander Cox (University at Buffalo)
• Kelly Anne Dakin (Alzforum, Boston)
• Paresh Dandona (University at Buffalo)
• Timothy Danford (Novartis, Boston)
• Peter D'Eustachio (Reactome / NYU School of Medicine, New York)
• Alexander Diehl (CL, GO / University at Buffalo)
• Fahim Imam (NIF / University of California at San Diego)
• Mark Jensen (University at Buffalo)
• Darren Natale (PRO / Georgetown University Medical Center, Washington DC)
• Mark Ressler (University at Buffalo)
• Caryn-Amy Rose (Alzforum, Boston)
• Alan Ruttenberg (University at Buffalo)
• Barry Smith (University at Buffalo)
• Kinga Szigati (University at Buffalo)
• Dominic M. Walsh (Brigham & Women's Hospital, Harvard Institutes of Medicine, Boston)
• Michael Wolfe (Brigham & Women's Hospital, Center for Neurologic Diseases, Boston)
• Cathy Wu (PRO / University of Delaware)
• Elizabeth Wu (Alzforum, Boston)