FROM INSIGHT TO OUTCOME DISEASE RESEARCH AT AGILENT

Transcription

1 FROM INSIGHT TO OUTCOME DISEASE RESEARCH AT AGILENT

2 UNDERSTANDING COMPLEX DISEASE PROCESSES Complex diseases, including cancer, cardiovascular disease, diabetes, and Alzheimer s disease, are caused by a combination of genetic, environmental, and lifestyle factors. Unraveling these factors and determining the underlying causes could lead to better prevention, diagnosis, and treatment, possibly including the development of personalized treatments based on an individual s genetic makeup. Given the complexity of human biology, researchers look for answers by studying the whole system. This can be achieved by integrating biological data from multiple omics (e.g., genomics, proteomics, and metabolomics) to reveal the relationships between genes, proteins, and metabolites and garner new insights into fundamental disease mechanisms. Agilent offers a wide range of LC/MS, GC/ MS, ion mobility MS, microarray, and next generation sequencing (NGS) solutions that enable human disease research. Our Integrated Biology software suite provides an interactive computing environment for rapid visualization and analysis of omics data. Placing data into biological context promotes deeper insights and Instrument Measurement Omics Data better understanding, helping you to test your hypothesis and formulate your next experiments with confidence. Agilent helps leading disease researchers understand the key factors in the biological systems they study. Our tools help leading researchers, like those featured here, remain on the forefront of disease research and they can do the same for you. Next Experiment Hypothesis Testing Data Processing & Analysis Genomics Metabolomics Biological Insight (Hypothesis) Transcriptomics Proteomics Data Integration & Biological Contextulization 2

3 INSIGHTS FROM PROTEOMICS Proteomics is the comprehensive study of proteins and their modifications (i.e., the proteome). Agilent provides solutions for protein identification and quantitation, glycan and glycoprotein analysis, phosphoprotein analysis, and protein biomarker discovery. Professor Stephen Pennington at University College Dublin is an expert in protein biomarker discovery. Biomarkers serve as early indicators of disease and they can be used to monitor disease progression, pharmacologic therapeutic response, and adverse responses to toxicants. He and his team are developing simple biomarkerbased blood tests including one to determine whether prostate cancer has remained localized or has spread, in order to guide appropriate treatment. He uses Agilent triple-quadrupole mass spectrometers and multiple reaction monitoring (MRM) of peptides to measure up to 100 proteins simultaneously and semi-quantitatively in patient samples. Agilent solutions have been critical to the development of a streamlined workflow for discovery of panels of proteomic biomarkers. Multiplexed targeted measurements using the 6490 are helping to advance our research; the robust and reproducible data generated on the 6490 provides highconfidence data extraction. PROFESSOR STEPHEN PENNINGTON, UNIVERSITY COLLEGE DUBLIN The Agilent 1290 Infinity LC and 6490 Triple Quadrupole LC/MS are shown here. 3

4 INSIGHTS FROM GLYCOMICS The main advantage of the Chip cube for glycomics applications is the ease of operation... This allows us to perform innovative research... ASSOCIATE PROFESSOR DIRK LEFEBER, RADBOUD UNIVERSITY MEDICAL CENTER Glycomics is the study of glycans sugars that are usually attached (glycosylated) to proteins or lipids. These macromolecules play critical roles in normal cell function and cellcell communication; abherrent glycosylation has strong disease implications. Associate Professor Dirk Lefeber, Nijmegen Center for Disorders of Glycosylation, is developing methods for glycan profiling. The aim of his research is to decode novel genetic factors that regulate the glycosylation process in patients with a rare gene disease. In this way, many disease symptoms could be linked with deficient glycosylation of proteins that lead to neuromuscular and neurodegenerative disorders. Dr. Lefeber utilizes the HPLC-Chip cube, interfaced with an Agilent 6540 QTOF mass spectrometer to embed glycomics methodology in his research. Agilent 1200-series nanoflow HPLC-Chip interfaced with the Agilent 6540 Quadrupole Time-of-Flight (QTOF) MS. 4

5 INSIGHTS FROM GENOMICS Agilent SureDesign and custom CGH+SNP microarray platform provide the flexibility that allows the detection of smaller genomic events... PROFESSOR YIPING SHEN, BOSTON CHILDREN S HOSPITAL At the Harvard Medical School and Boston Children s Hospital, Professor Yiping Shen is working to uncover the role of abnormal CNVs in epilepsy and to identify the genes that might provide novel candidate therapeutic targets. When catalog whole genome microarrays did not meet his research needs, Dr. Shen worked with Agilent, using SureDesign, to develop a custom CGH + SNP microarray that enabled detection of CNVs at higher resolution and with better specificity than catalog arrays. Agilent Custom CGH + SNP Microarray Platform can be combined with Agilent SurePrint technology to design and print user-defined CGH + SNP microarrays to detect CNVs and copy neutral aberrations in the same array. 5

6 INSIGHTS FROM METABOLOMICS Support from Agilent has allowed us to expand our analytical capabilities, leveraging their state-of-the-art targeted and untargeted mass spec platforms. PROFESSOR ROBERT GERSZTEN, HARVARD MEDICAL SCHOOL, DIRECTOR OF RESEARCH AT MASSACHUSETTS GENERAL HOSPITAL HEART CENTER Metabolites are biochemically active small molecules. Long thought simply to be metabolic by-products, a growing body of evidence suggest that metabolites are active participants and regulators in disease pathogenesis. Dr. Robert Gerszten at Massachusetts General Hospital and Harvard Medical School is a recognized leader in cardiovascular research and biomarker discovery. He leads a metabolite profiling study of well-phenotyped human populations, including data from the Framingham Heart Study. His research is focused on identifying new metabolites and proteins that mark disease activity, signal disease progression, and ultimately provide targets for therapeutic intervention. His work combines metabolomics and proteomics, using an Agilent 6550 LC-QTOF for untargeted (discovery) work and an Agilent 6490 LC-Triple Quadrupole mass spectrometer for targeted studies. Data Acquisition Feature Finding Alignment and Statistical Analysis Identification Pathway Analysis MassHunter Software Mass Profiler Professional Software Analytical Instruments Qualitative Profinder Analysis and visualization ID Browser using Agilent METLIN Database and Agilent Fiehn Library Pathway Architect using public databases, such as KEGG Agilent supports both untargeted (discovery) and targeted metabolomics solutions with a unified data analytics platform across LC/MS, GC/MS and SFC/MS metabolomics workflow solutions. 6

7 INSIGHTS FROM MULTI-OMICS (INTEGRATED BIOLOGY) Dr. Junying Yuan, of Harvard Medical School, heads up the Chinese Academy of Science s Interdisciplinary Research Center on Biology and Chemistry. Dr. Yuan and her team are studying metabolite protein, protein protein, and genetic networks involved in the etiology of neurodegenerative disease. They are using Agilent s 6550 LC/ MS system for large-scale, high-throughput profiling, identification, characterization, and quantitation of proteins, metabolites and their interactions along with Agilent s Integrated Biology software suite. The Integrated Biology (IB) software suite includes GeneSpring, Mass Profiler Professional, and Pathway Architect. These individual modules jointly process data from genomics, NGS, transcriptomics, proteomics, and metabolomics and enable mapping of individual entities onto their corresponding canonical biological pathways. The IB suite offers an intuitive, highly interactive environment that doesn t require specific expertise to use. Researchers can translate experimental outcomes to meaningful, relevant biological understanding. Integrating our metabolomics data with transcriptomic and proteomic data will allow us to better study disease pathogenesis by more fully understanding underlying disease biology. Our aim is to identify five to ten protein targets or biomarkers for neurodegenerative diseases within the next three years. PROFESSOR JUNYING YUAN, HARVARD MEDICAL SCHOOL The Agilent GeneSpring software suite enables you to integrate and analyze multi-omics data. Providing powerful statistics and visualization, it gives biological context to your data. 7

8 Learn more Find a local Agilent customer center USA and Canada agilent_inquiries@agilent.com Europe info_agilent@agilent.com Asia Pacific inquiry_lsca@agilent.com For Research Use Only. Not for use in diagnostic procedures. This information is subject to change without notice. Agilent Technologies, Inc., 2015 Printed in the USA, September 26, EN