Comparing apples to Apples

IO Informatics and Sage-N Research announce partnership to discover potential biomarkers, disease causes and prevention

Lloyd Dunlap
SAN FRANCISCO—IO Informatics, a leader in semantic dataintegration and knowledge management for life sciences and healthcare, willpartner with Sage-N Research Inc., a company that specializes in computationalproteomics, in an agreement announced last month.
 
 
The combination of the two companies' technologies creates asemantic application framework that is being used to quickly develop a highlyspecialized, large-scale application that leverages mass-spectrometry basedproteomics with "unmatched content enrichment, interoperability and flexibilityonly possible with semantic data integration," the release announcing thepartnership states.
 
"Semantic data integration means putting data in context,"explains Dr. Erich Gombocz, IO's chief scientific officer. "I use the exampleof an apple. 'How much does an apple cost?' is totally dependent on if you meanthe fruit or the computer; without that context, you really cannot answer thisquestion. The same holds true in a much more stringent way for biological data;data out of context is isolated and of no actionable use, but data in contextof other data provides the meaningful underlying framework to understandcomplex interactive and interrelated intricate biological processes on asystems level. Because our technology is based on the Resource DescriptionFramework, its data structure does not require predefined schemas, but is basedin its entirety on triples—sets of resources commonly described in form of 'Ais related to B' (or, more formally, as subject, predicate, object). Databecomes aware of their surroundings—they are 'sentient' of how to connect andwhat they mean in their context, thus the name of IO's tools, 'Sentient Suite.'Because of this dynamic extensible and data-container agnostic framework, datacan be mapped to ontological concepts and are easily reconfigured to changingscientific needs." 
 
 
Most importantly, Gombocz believes, since a semanticknowledge base is a network graph of data in their relationships with eachother, it enables discovery of pattern-based relationship clusters andinteractions that were not previously apparent. Graphic icons representproteins, diseases and organisms, for example, with the colors and thicknessesof connecting lines indicating relative strength of the relationships.
 
 
The technology also allows users to infer and reason acrossthe graph, and to create pattern-based queries containing, for instance,signatures for a specific biological function (such as biomarkers used asdisease profile for a certain stage of a disease or a certain demographicpatient group with a specific genetic profile).
 
 
"With the ever-growing Linked Open Data (LOD) in semanticformat, IO's technology provides tools to build and enrich knowledge bases forspecific user needs—such as liver toxicity categorization, comparativeeffectiveness of cancer treatments, risk assessment of organ transplantfailures or differentiation of stable versus ruptured plaques in cardiacdiseases, which are all cases where IO has applied its technologies in thepast. This way, knowledge is never stale; it can keep pace with scientificadvances, and is actually actionable—you can use it as decision support inscreening and diagnostic or therapeutic applications," Gombocz says.
 
 
Currently, there are about 45 public databases in use by IOthat contain information on organisms, pathogens, genes and proteins.
 
 
"One application of this novel approach is to identifypeptides from different microorganisms with a common mechanism of actions, andto categorize them as potential biomarkers, and it also has the capability todetect microbial threats prior to onset of disease symptoms," says Ali Pervez,vice president of marketing at Sage-N Research.
 
 
"Future applications of this technology will enableautomated screening for biological threats, to characterize origin and type ofdisease and to develop preventive measures (drugs or vaccines) effective forseveral classes of microorganism," adds Robert Stanley, president of IO.
 
 
"Together with IO's semantic knowledge base concept,Sage-N's Sorcerer and IO's Sentient Knowledge Explorer and Sentient WebQueryallow us to pre-package entire knowledge bases of biological systems through meaningfulinterconnection of experimental and public data resources under a commonarchitectural framework," Gombocz notes. "The partnership has been a logicalsynergistic extension of capabilities through combination of innovation fromboth sides. IO Informatics, together with its collaborators and customers, hasbeen instrumental in the arena of biomarker discovery and qualification, andSage-N has been leading in spectra-based ID research for microbial pathogens.The partnership extends the efforts towards a deeper understanding of peptide-and protein-related mechanistic impact on disease-related pathways based onsystems biological network views—all areas which require expertise inhigh-throughput workflows, scalability and dynamic knowledge building towardsreal-time actionable applications which account for alerting and decisionsupport via web and mobile platforms."
 

 

 
Sage-N teams with Pressure BioSciences onanalysis of cell membrane proteins 
 
SOUTH EASTON, Mass.—Sage-N Research Inc. also announcedMarch 19 that it will collaborate with Pressure BioSciences Inc. (PBI) todevelop software applications on Sage-N's SORCERER Integrated Data Applianceplatform. The new software will be designed to work with PBI's patented andenabling pressure cycling technology (PCT) system, a technology platform thatis used to extract, among other biomolecules, integral cell membrane and otherproteins for subsequent mass spectrometry analysis.
 
 
According to the companies, these proteins are of significantclinical importance due to their roles in cell signal transduction in cancer,membrane transport disorders like Crohn's disease, pathogen invasion such asHIV and their roles in other diseases and disorders. Unfortunately, integralcell membrane proteins are traditionally very difficult to extract. In somecases, harsh chemicals are used in the extraction process, causing such severeprotein degradation that subsequent proteomic analysis is compromised.
 
 
PBI's PCT platform uses rapid cycles of low and ultra-highpressure to safely and effectively extract proteins from samples (includingcell membranes) that are suitable for analysis by analytical methods such asmass spectrometry. The PCT platform also provides a high level of automation,speed and reproducibility in the enzymatic breakdown of proteins. This allowsthe PCT-enhanced digestion to be completed in under an hour, compared to thestandard four to 12 hours, according to PBI.
 
Sage-N's SORCERER Integrated Data Appliance platformprovides complementary software applications that are customized for eachparticular sample preparation chemistry. This results in a semi-automatedsystem for membrane and other protein analysis that can use any modern tandemmass spectrometer and liquid chromatography system, says Sage-N. 
 
"We plan to seamlessly integrate PBI's front-end PCT SamplePreparation System—instruments and consumables—with Sage-N's SORCERER back-enddata reduction software," explains Richard T. Schumacher, president and CEO ofPBI. "We expect to offer this bundled platform as an option to stand-alonesample preparation and data reduction methods used currently by the massspectrometry laboratory. We believe that by bundling these enabling platforms,we will be offering a higher quality, more efficient and less costly solutionthan they currently have for sample preparation and data reduction. Since thecompanies now target an identical market—the mass spectrometry laboratory—weexpect to share a number of marketing and selling programs directed at thismarket going forward. Overall, we believe our new co-marketing program willreduce costs and increase sales for both PBI and Sage-N before the end of2012."
 
 

Lloyd Dunlap

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