PRO Use Cases for Scientific Communities

Paolo Ciccarese
Paolo CiccaresePrincipal Informatics & Knoweldge Engineer at Innovation Lab
Semantic Resources ProjectPRO (Protein Ontology) Use Cases for Scientific Communities,[object Object],Paolo Ciccarese, PhD,[object Object],Mass General Hospital,[object Object],  Harvard Medical School,[object Object]
Semantic Resources Project	,[object Object],Collaboration between,[object Object],Mass General Hospital,[object Object],Science Commons,[object Object],Alzforum,[object Object],Goal: creating a set of semantic resources,[object Object],Of interest for SWAN and SCF projects ,[object Object],Following best practice,[object Object],Two examples of PRO related resources:,[object Object],Proteins of interest in AlzSWAN (APP, Tau, Synuclein),[object Object],Antibodies (immunogens and antigens) ,[object Object]
SWAN (Semantic Web Application in Neuromedicine),[object Object],It is a Web-based collaborative program that aims to organize and annotate scientific knowledge about neurodegenerative disorders.,[object Object],Collaboration of Mass General Hospital with Alzforum(www.alzforum.org),[object Object],Its goal is to facilitate the formation, development and testing of hypotheses about neurodegenerative diseases.,[object Object],It is about scientific discourse,[object Object],http://swan.mindinformatics.org,[object Object]
AlzSWAN (SWAN for Alzheimer),[object Object],http://hypothesis.alzforum.org,[object Object]
AlzSWAN Curation Process,[object Object],SWAN: browser,[object Object],1. reading,[object Object],Curator,[object Object],5. publishing,[object Object],2. extracting,[object Object],4. connecting,[object Object],Hypothesis ,[object Object],Discourse List, Citations,[object Object],Genes, Proteins,[object Object],3. organizing and ,[object Object],encoding,[object Object],SWAN: workbench,[object Object]
Hypothesis list,[object Object],http://tinyurl.com/27sh3ta,[object Object]
Hypothesis,[object Object],http://tinyurl.com/2c3lhzn,[object Object]
Hypothesis,[object Object],http://tinyurl.com/2c3lhzn,[object Object]
The hypothesis graph,[object Object]
AlzSWAN proteins management,[object Object],When the curators need a new protein they import it automatically from UniProt,[object Object],Data are stored according to the SWAN LSEs Ontology (http://swan.mindinformatics.org/spec/1.2/lses.html),[object Object],UniProt does not give access to all the info we need (isoforms, cleavage products…),[object Object],Willing to use PRO ontology and others when available (and demonstrate to cover our needs),[object Object],http://swan.mindinformatics.org/spec/1.2/lses.html,[object Object]
AlzSWAN,[object Object],[object Object]
Protein post-translationally modified have distinct roles:
Protein isoforms from a single gene have different physiological vs. pathological functions
Cleavage products have functions distinct from the parent protein
Example: APP protein Abeta peptides, soluble APP, AICD
Proteins are assembled into protein complexes, and these are affected by isoform and post-translational modification
Example: Tau protein: how many microtubule binding domains (which exons used from gene), phosphorylation state of protein affect MT binding or fibril formation
Example: Abeta peptides form dimers, oligomers, amyloid plaqueSWAN Proteins:  Gwen Wong & Elizabeth Wu (Alzforum),[object Object]
APP is a gene that encodes a complexity of proteins,[object Object],[object Object]
Multiple splice variant mRNAs
Mulitiple protein isoforms expressed
Some isoforms are ubiquitous, others neuron specific or T cell-specific
Variety of conserved functional domains throughout length of protein
Isoform differences in major domains may have functional consequences
APP interacts with multiple proteins
Mutations throughout protein associated with familial Alzheimer Disease
Cleavage products generated by α-, β- and γ-secretase are involved in both normal and pathogenic protein functions.SWAN Proteins:  Gwen Wong & Elizabeth Wu (Alzforum),[object Object]
SWAN Protein Ontology is NOT ,[object Object],just for APP,[object Object],SWAN Proteins:  Gwen Wong & Elizabeth Wu (Alzforum),[object Object]
Summary of SWAN needs,[object Object],[object Object]
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PRO Use Cases for Scientific Communities