neuro gem
TRANSCRIPT
NeuroGem, a knowledgebase of genetic modifiers in neurodegenerative diseases
Dokyun Na, Mushfiqur Rouf, Cahir O'Kane, David C Rubinsztein and Jrg Sponer
Presented byAnjani K DhrangadhariyaJunior Student, MS Life Science InformaticsBonn Aachan International Institute of Information TechnologyUniversitt Bonn
Terms
Knowledge base: a special kind of database for knowledge management. A knowledge base provides a means for information to be collected, organized, shared, searched and utilized.
Genetic modifiers: genes that have small quantitative effects on the level of expression of another gene.
Neurodegenerative disease: Progressive loss of neurons in human brain
http://www.ndsu.edu/pubweb/~mcclean/plsc431/mendel/mendel7.htm
http://helpdeskhelps.com/education/what-is-a-knowledge-base/
PubMed: NeuroGem
Unabridged data
Majority of neurodegenerative diseases are sporadic.
However, strong genetic components linked to ND's identified.
Recent times show significant efforts not only in identification of disease causing genes but also the ND modifying genes.
So you have lots of experimental data which identifies numerous genetic modifiers in different organisms in different NDs. What will you probably do if you want to find new knowledge from all these experiments?
Building the bridge
But till date there exists no compedium that lists or crosslinks genetic modifiers of different ND's
First knowledgebase providing integrated information on genetic modifiers of 9 different NDs.
Improve the approaches to discover what is common to and distinct for different proteinopathies
Characteristics of NeuroGem
Detailed information on experimental condition
Protein-protein interaction sub-network around modifier
Search and display tool
Search for orthologs of human and mouse genes
Includes both high throughput and low throughput data
Users can submit their data on request
Construction and content
Data Collection3 model organisms
9 disease models
Modifiers from variety of diseases
Total experimental records = 87,864
Modifiers = 3,618
Non-modifiers = 84,246
Contents of NeuroGem
Content description
Modifier gene information taken from
Has link for PubMed entry of original study
Protein interaction data from
Facilitate searching genes with same function or if they were involved in same process by incorporating data from
Searching homologs of human and mouse
Gene information, GO annotations, interaction data
DB implementation
Implemented with interface compatible with common web browsers.
Data is stored in RDBMS (MySQL 5.0.59 server)
Improvement of search functions: Javascript and Ajax
HTML generation for displaying information using PHP 5.3.3
Protein-protein interaction network: cytoscape
Current database running on Redhat Linux 5.6
Utility and discussion
Data from NeuroGem can be accessed in 3 different wayA categorical search (category-wise)
Keyword-based search (specific genes)
Ontology based search (For related genes)
Genetic modifier information
At the end of any search, users are directed to genetic modifier information page.
Search for orthologs of Human and Mouse genes
Does not contain any information on genetic modifiers of human and mouse.
However researchers are obviously interested in homologous modifier genes in higher organisms
Broad applicability
To demonstrate broad applicability of NeuroGem and how it provided with new understanding, a variety of meta analysis were performed.
Identify biological processes that are enriched with certain modifiers
Pathways enriched with certain genetic modifiers. Protein folding, cell cycle and splicing.
Researchers can focus on this pathways
HD, generic polyQ, SCA1, SCA3, SCA7 share genetic modifiers not seen in AD
SCA3 = Protein folding and splicing
AD (abeta) = protein synthesis
Identify genes that modify toxicity of several neurodegenerative disorders
Cross disease comparisions can reveal generic modifiers
These generic modifiers can then be tested for in other disease models in other organisms.
Dnaj-1 and BIRC3(thread) shown o reduce neuronal death when upregulated
Atx2 associated with increased risk of ALS
Identification of unique modifiers
Although they are all caused by agrregates
Each ND has different pathophysiology
Example, modifiers confined to AD(Tau) in D. melanogastor are sgg and par-1.
New insights into mechanism of disease modulation
HD: D. MelanogastorAnalysed modifiers and classified according to GO
Aggregate enriched: Protein folding and splicing
Toxicity enriched: Cell cycle, cytoskeleton and protein folding
PD: C. elegansAggregate enriched: Proteolysis
Toxicity enriched: Protein folding, Signaliing
Hence, aggregation modifiers support the formation of aggregates & toxicity modifiers regulate cell tolerance.
Interesting finding!
From HD modifiers, 20 genes enriched in both categories were taken taken and it was identified that the groups include Dnaj-1, thread and Atx2.
Not only these are generic but are also most enriched.
Conclusion
First compedium that catalogous and cross-links genetic modifiers.
Can be utilized for searching and retrieving modifiers, predicting roles of a modifier, visualize surrounding network of modifier, analyse homologous genes from human and mice.
Allows users to evaluate their hypothesis and develop new research directions.
Data in NeuroGem is in downloadable form so other meta analysis can be conducted
Seriously! I need a constructive feedback
Was I too loud?
Was it too fast?
Anything that I can improve...
Thank You