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The Ongoing Collaboration Aims to Exploit the High Throughput, Robustness and Ease of Use of MALDI-TOF Instruments

At the 12th HUPO World Congress, Bruker Corporation (NASDAQ: BRKR) recently announced the start of a second-phase collaboration agreement with SISCAPA Assays Technologies, Inc. (SAT). The ongoing collaboration aims to exploit the high throughput, robustness and ease of use of MALDI-TOF instruments as an alternative to nano-LC-MS technology currently used in many SISCAPA assays.

AB SCIEX Proteomics Scientist Wins HUPO 2013 Science and Technology Award

The Human Proteome Organization (HUPO) recently awarded Christie Hunter, Ph.D, director of proteomics applications at AB SCIEX, its 2013 Science and Technology Award at an award ceremony during last week’s HUPO 2013 conference in Japan. Dr. Hunter was recognized for her contributions to the development and commercialization of a breakthrough approach for targeted proteomics. The analytical strategy of targeted proteomics was recently named “Method of the Year” by Nature Methods.

Targeted proteomics is a standardized, biological research workflow that focuses on reproducibly quantifying a specific subset of proteins within a sample. It generates data that is vital for biologists to answer hypothesis-driven, biological questions.

A decade ago, proteomics research was dominated by discovery workflows, which provided valuable information on a single sample but lacked the reproducibility to generate robust quantitation across a larger sample set. New innovation was needed at the time to move the field beyond simply producing large lists of identified proteins and toward providing highly quantitative answers.

This led to the development of a multiple reaction monitoring (MRM)-triggered, tandem mass spectrometry (MS/MS) workflow at AB SCIEX to rapidly create high sensitivity MRM assays to target peptides that are unique to their associated proteins. This workflow was made possible by the combination of triple quadrupole and linear ion trap functionality in a single system called the AB SCIEX QTRAP® System.

Dr. Hunter ‒ in collaboration with researcher Dr. Leigh Anderson, the founder of the Plasma Proteome Institute and head of SISCAPA Assay Technologies ‒ pioneered a workflow that applied MRM to the targeted quantification of proteins and peptides in plasma by mass spectrometry. In their initial publication[1], Dr. Hunter and Dr. Anderson demonstrated that a targeted workflow could be applied to multiplexed quantitation of proteins in human plasma with high reproducibility and high confidence in the results.

The impact of the paper resulted in broad adoption of the MRM technique around the world to accelerate the verification and validation of putative protein biomarkers, generating more than 800 citations, according to Google Scholar. Less than a decade after this important work, most proteomics laboratories today use a triple quadrupole-based mass spectrometer to perform MRM analysis.

“We congratulate Dr. Christie Hunter on receiving such a prestigious award from HUPO in recognition of her significant contributions to the rise of targeted proteomics as a viable technique to advance biomarker research,” said Dave Hicks, Vice President and General Manager of the Pharmaceutical and Academic Business at AB SCIEX.

“Dr. Hunter and her AB SCIEX colleagues continue to participate in exciting collaborations with leading proteomics researchers around the world to drive new innovations in software, chemistries and instrumentation that further expand quantitative proteomics workflows for the growing community of mass spectrometry users at large,” added Hicks.

Currently, Dr. Hunter is playing a pivotal role in the development of higher specificity workflows for targeted protein quantitation to overcome situations where sensitivity is limited by interferences or background. She is involved in the investigation of the utility of differential mobility separations for added selectivity of quantitation of peptides in complex mixtures. She is also working to enhance data-independent acquisition strategies, such as SWATHTM Acquisition, for quantitative proteomics to increase the multiplexing and reproducibility that can be achieved in a single experiment.

Source: AB SCIEX

SAP and Technical University Munich Decode Human Proteome and Make Data Available for Biomedical Research

SAP AG (NYSE: SAP) and Technical University Munich (TUM) recently announced ProteomicsDB, a new offering based on the SAP HANA® platform that stores protein and peptide identifications from mass spectrometry-based experiments. The proteomic data assembled in the new offering resulted in the identification of proteins mapping to over 18,000 human genes. This represents 90 percent coverage of the human proteome. Data stored and analyzed within ProteomicsDB can be used in basic and biomedical research for discovering therapeutic targets and developing new drugs as well as enhanced diagnosis methods.

As personalized medicine is on the rise, the healthcare field is discovering the opportunities of big data analysis. The result of a joint project between the TUM Chair of Proteomics and Bioanalytics, SAP and the SAP Innovation Center, ProteomicsDB is a major step forward in human proteomics. It currently contains more than 11,000 datasets from human cancer cell lines, tissues and body fluids and enables real-time analysis of this highly dimensional data and creates instant value by allowing to test analytical hypothesis.

ProteomicsDB is based on the SAP HANA for rapid data mining and visualization. It has been built to enable public sharing of mass spectrometry-based proteomic datasets as well as to allow users to access and review data prior to publication. The database is backed with 50 TB of storage, 2 TB RAM and 160 processing units. A direct interface to the programming languages L, C++ and R allows more flexible calculations than are possible with standard SQL. The Web interface is built on a JavaScript framework for HTML5 and optimized for Google Chrome but also available under Internet Explorer and Mozilla Firefox. An easy-to-use and fast Web interface allows users to browse and upload data to the repository as well as browsing the human proteome, including protein level information such as protein function and expression.

ProteomicsDB will be available free of charge. The database will be a valuable asset for researchers in the field of life sciences as well as for the pharmaceutical and biotechnology industry. Insights from analyzing the inherent datasets can be used in biomedical research and for example in developing new drugs that operate in a more targeted way without adversely influencing other cellular processes, helping to reduce side effects.

“The vast amounts of molecular data generated in biomedical research increasingly challenge the ability of scientists to see ‘the forest for the trees,” said Prof. Dr. Bernhard Kuster of TUM. “ProteomicsDB is a significant step ahead in our research aiming at a better understanding of human disease and more informed future treatments. The software helps us and others to store, integrate and analyze experimental data in real time, allowing us to study more complex biological systems at greater depth than previously possible.”

Source: SAP

Kinexus Identifies Over 966,000 Phosphorylation Sites in the Human Proteome

Kinexus Bioinformatics Corporation, a world-leader in molecular intelligence research, announced a major upgrade in its PhosphoNET KnowledgeBase (www.phosphonet.ca) for the study of cell communication systems. This open-access website now features data on over 177,000 experimentally-confirmed human phosphorylation sites (P-sites) and 789,000 additional P-sites predicted with a powerful algorithm trained with over 22,000 kinase-substrate pairs. PhosphoNET provides prediction of which kinases individually target each human P-site, and whether these P-sites are retained in proteins from over 20 other diverse organisms. Functionally critical P-sites that control proteins are more likely to also be found in other species. This information can guide biomedical researchers in the discovery of promising diagnostic biomarkers and therapeutic drug targets.

The Institute for Systems Biology and AB SCIEX Partner to Help Make Medical Care More Predictive and Personalized

Medical care is expected to become more personalized and better able to help prevent the onset of diseases in the future, thanks to groundbreaking research into P4 medicine underway by world-renowned scientists at the Institute for Systems Biology, including National Medal of Science award winner Leroy Hood, MD, PhD., and ISB proteomics research director, Robert Moritz, PhD., and now supported by a new collaboration with AB SCIEX, a global leader in analytical technology.

ISB and AB SCIEX have signed a multi-year agreement to collaborate on the development of methods and technology in proteomics mass spectrometry with the goal to redefine biomarker research and complement genomics through fully comprehensive quantitative proteomics analysis. This will help advance the development of a new approach to medical care.

ISB’s concept of P4 medicine promises to provide deep insight into disease mechanisms on the path to develop medical care that is predictive, personalized, preventive and participatory (the four “P”s) – a pioneering vision that requires a combination of analytical tools, workflows, databases, collaborations and computational strategies.

“With breakthroughs in translating research into clinical relevance, P4 medicine is expected to enable the creation of a virtual cloud of billions of data points around each individual as the basis for straightforward predictions about health and disease,” said Dr. Hood, ISB president and co-founder. In December, he was named a recipient of the National Medal of Science, which is the highest honor the President of the United States can bestow on a scientist, in recognition of visionary work for the advancement of science.

Led by Dr. Hood, ISB’s groundbreaking research is being accelerated by SWATH™ Acquisition, a data-independent acquisition (DIA) mass spectrometry workflow that can quantify virtually all detectable peptides and proteins in a complex sample – all in a single analysis.

“Quantifying enormous numbers of protein analytes at the same time is a critical need to accelerate P4 medicine and the democratization of proteomics, a revolution that is akin to the sequencing of the genome and the democratization of DNA,” added Dr. Hood. “SWATH is a game-changing technique that essentially acts as a protein microarray and is the most reproducible way to generate comprehensive quantitation of the entire proteome. It generates a digital record of the entire proteome that can be mined retrospectively for years to come.”

ISB’s know-how in systems biology and informatics will support the development of SWATH libraries, similar to its highly regarded SRMAtlas project for the human proteome, pioneered by Rob Moritz and his collaborators, and the proteomes of other clinically-relevant organisms. “With complete proteome-wide libraries, ISB provides the basis to support comprehensive SWATH analysis,” said Dr. Moritz, ISB Proteomics Research Director.

Committed to an open policy of sharing data and methods, ISB will make the SWATH libraries available to the global scientific community to accelerate the use of SWATH for other biological research. Utilizing the depth in proteomics technology development and underpinned by the extensive proteomics computational resources in data interpretation tools, standards initiatives and database development under the leadership of Dr. Moritz, ISB will develop new SWATH technologies and tools to enable the community to quickly adopt comprehensive quantitative proteome analysis.

“Having the proteomics data standardized across laboratories and across samples really enables us to quantitate entire proteomes at a level that hasn’t been done before,” said Dr. Moritz. “We aim to define markers that can predict whether a patient will respond to a certain treatment or not, and applying SWATH will play a big part in taking our advancements to another level. Not only can we now complement the breadth of genomics, but we will have the much-needed libraries and software development going forward to make data-sharing quite easier and standardized.”

As a trusted partner with academic researchers, AB SCIEX has formed this strategic alliance with Dr. Hood, Dr. Moritz and their distinguished ISB colleagues through the AB SCIEX Academic Partnership Program to help broaden the availability of new technologies to researchers delving into omics research around the world.

“What ISB does with SWATH will set a new benchmark in proteomics research,” said Rainer Blair, President of AB SCIEX. “Our collaboration with ISB will help drive SWATH into the mainstream of analytical science and make comprehensive, reproducible and simplified omics data more accessible to biologists around the world.”

ISB will be using the AB SCIEX TripleTOF® 5600± System and an Eksigent ekspert™ nano-LC 400 System as the instrument platforms on which to conduct the protein identification and quantitation. The TripleTOF 5600+ System provides the high speed necessary for SWATH Acquisition. TripleTOF technology combines high speed and high sensitivity with high resolution and accurate mass. ISB also plans to use SelexION™ technology, a recent advancement in differential ion mobility, in the future to advance its research.

Source: Institute for Systems Biology