Accelerating the Implementation of Mass Spectrometry in the Clinical Lab

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UNITED STATES 2019

Help Us Reach Our Educational Support Goal of $40,000
Educational Grants supported in part by:
Brian Kelly
Danyel Tacker
Amadeo Pesce

Plenary & Keynote Lecture Series


Distinguished Contribution Award Lecture


On the Award

>> Wednesday 17:30 in Rm 2-4
Immunotherapy of Cancer and the Role of Mass Spectrometry; An Overview and New Results
Donald Hunt
University of Virginia

This lecture will describe how the immune system works to keep us free of cancer most of the time and how cancer cells can eventually learn to escape the immune system. Also described will be a number of scientific breakthroughs that have occurred in the last 6 years that clearly suggest that the immune system can be re-educated and upregulated to cure even late stage cancer. Science magazine labeled cancer immunotherapy as the breakthrough event of the year in 2013 and tremendous progress has been made since then. James Allison won the 2015 Lasker Award and shared the 2018 Nobel Prize in Medicine with Tasuku Honjo for their work to reactivate the immune system to fight cancer. This lecture will try capture some this excitement and also pinpoint some of the contributions that the Hunt group has made to the field over the past 25 yrs.

Plenary Lectures


>> Tuesday 14:15 in Rm 2-4
Analysis of Exosomes from Patient Serum Samples : Proteomic, Metabolomic and Lipidomic Analyses
David Lubman
University of Michigan Medical Center

We have isolated exosomes from the serum of ten patients with locally advanced pancreatic cancer at serial time points over a course of therapy. We have explored several different methods to purify exosomes in patient serum where it is essential to remove serum proteins including albumin for proteomics studies. Exosomes were identified by using quantitative mass spectrometry. We compared the exosomal proteome of patients at different time points during treatment to healthy controls and identified 8 proteins that show global treatment-specific changes. More recently we have studied changes in the serum exosome metabolome during therapeutic treatment where specific metabolites and lipids may be markers of treatment. The differential content of exosomes during a course of therapy suggests that exosomes may provide novel insights into the development of treatment resistance and metastasis.
>> Thursday 15:30 in Rm 3-4
Tools and Infrastructure to Enable Crowdsourcing the Molecular Analysis of Microbiome as Applied to Precision Care
Pieter Dorrestein
University of California, San Diego

The general community is encouraged to visit the same primary care physician. This is because they “know” their patients. This means that when the physician observes changes or upon request of the patient, a physician may request additional tests to be performed such as measuring small molecules. Cholesterol, lipids, thyroid hormones, and serotonin levels are representative examples. If these molecules are out of the norm, or dramatically change from previously measured levels, an intervention may be prescribed. In recent years OMICS technologies, including informatic capabilities, have advanced significantly and has led to the increasing recognition that a person is a walking ecosystem not only comprised of human cells but also bacteria, fungi and other eukaryotes and phages, collectively called the microbiome. In addition that when the microbiome defines the health and disease status of the host as well as how a patient responds to interventions such as medications. Monitoring the changes due to the microbiome is difficult but, in principle, if we can perform untargeted OMICS analysis of patient samples, it can be expected that such monitoring can be used by physicians to understand their patients. This presentation describes how research grade untargeted mass spectrometry and microbiome sequencing based OMICS technologies can be used to understand the disease and the effect of treatments. This is achieved through building crowd sourced community knowledge capture, analysis, and data visualization infrastructures and apply them via close interactions with physicians. The ability as will be highlighted in this presentation via providing large scale data analysis and visualization capabilities at clinical relevant time scales represents the tip of the iceberg of what future technologies may bring. We will showcase these capabilities through highlighting the early versions of these capabilities that has processed 100,000s of samples. Examples will be shown associated with inflammatory diseases, liver disease, metabolism, cardiac disease, infectious disease, sleep deprivation, malnutrition but also several single patient case studies, including a single patient phage therapy treatment.

Keynote Lectures


>> Thursday 9:00 in Track 5 (Room 4) : Session 5
The Skyline Software Ecosystem: Efforts to Achieve Transparency, Interoperability, and Robustness of Quantitative LC-MS Assays
Michael MacCoss
University of Washington
Skyline is a freely-available and open source Windows client application for building quantitative LC-MS methods and the analysis of the resulting mass spectrometry data. We have applied state-of-the-art technologies for creating methods, iteratively refining assays, and the visualization of quantitative mass spectrometry experiments across all major instrument vendors. Originally Skyline was developed specifically for targeted proteomics but has expanded to support method development and data analysis for all molecular species. There have been over 90,000 new installations of Skyline since it was first publicly released at ASMS 2009, with 1000 installations on average each month over the past 6 months, and consistently >8000 software boot-ups per week for the last year. Additionally, Skyline supports an external tool framework with 13 tools available currently (some with >10,000 installations themselves). The server side project Panorama (http://panoramaweb.org), supports managing Skyline documents (both results and assay validation), sharing data within a group or to the entire community, and real-time collection and tracking of instrument system suitability data. Recent capability like quantitative signal calibration, assay figures of merit, and audit logging have been developed in close collaboration and with iterative feedback with members of the MSACL community. I will present a perspective on the history of the project, provide examples of how these tools have been used in assay development, and provide a vision for the future.
>> Wednesday 9:00 in Track 1 (Pueblo) : Session 1
MALDI Imaging MS: Transforming Drug Discovery and Development Through Molecular Images of Biological Systems
Steve Castellino
GlaxoSmithKline
The application of MALDI IMS in drug discovery and development has evolved from providing “snap shots” of drug and drug metabolite tissue distributions to addressing the more fundamental questions pertaining to quantitative disposition, validation of delivery strategies, and understanding the complex mechanistic relationships between molecular initiation events of pharmacologically active compounds and the cascade of biological consequences. Cumulative IMS experimental data of disease states and pharmacology models have been transformational in building and expanding our knowledge on drug delivery, disposition, pharmacology and underlying mechanisms of disease. This knowledge is critical in translating results from in vitro and in vivo models into safe and efficacious medicines to meet the medical needs of a diverse population. This presentation will include examples from early and late stage medicinal development where MALDI IMS has had a significant impact on our understanding of pharmacology and mechanisms of disease states.
>> Wednesday 11:00 in Track 6 (Room 5) : Session 2
Towards Automated Quality Assessment and Analysis of Targeted Mass Spectrometry Data using Machine Learning
Shadi Eshghi
Genentech

Targeted mass spectrometry has enabled highly multiplexed and sensitive quantitation of lipids, metabolites and protein biomarkers for clinical research and development. The increased rate of data production along with the need for improving data processing efficiency and reproducibility has created growing demand for automated analytical tools in the field. We have developed TargetedMSQC, an open source R package that takes advantage of machine learning for semi-automated quality assessment of chromatographic peaks in targeted MS data. The workflow of TargetedMSQC and its application for analysis and quality control of large datasets including clinical trial biomarker data will be discussed.
>> Wednesday 15:00 in Track 6 (Room 5) : Session 4
Maximizing the Performance of MALDI-TOF MS-based Microbial Characterization: Challenges, Strategies, and Successes Beyond Species-level and Pure Culture Applications
Todd Sandrin
Arizona State University

Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) has emerged over the past decade as a rapid and accurate alternative to traditional methods of microbial characterization in the clinical laboratory. Countless successes have been reported with species-level identification of diverse microorganisms of clinical and environmental importance, but challenges have been described in the literature when applying the method at taxonomic levels beyond the species level (e.g., at the strain level). Furthermore, application of MALDI-TOF MS has largely been restricted to pure cultures of bacteria. Our group has developed and optimized strategies to enhance performance of MALDI-TOF MS-based approaches at the strain level and with polymicrobial mixtures. Collectively, our results suggest that maximizing performance beyond the species level and with polymicrobial mixtures requires rigorous optimization and standardization of culture conditions, sample preparation methods, data acquisition modes, and data analysis approaches.
>> Thursday 11:00 in Track 4 (Room 3) : Session 6
Translation of Lipidomic Technologies Towards Quantification of Blood Lipids
Marcus Wenk
National University of Singapore

The main elements of lipidomic technologies are now available and ready for adoption in larger scale studies. However, the translation of laboratory-style methods for lipid measurements – based on mass spectrometry – towards robust, quantitative tests that deliver comparable results across different analytical sites and with appropriate turn-around times will require considerable extra efforts. Here I will introduce our model for engagement which we have been pursuing with the Singapore Lipidomics Incubator (SLING) at the National University of Singapore (NUS). Examples, in the context of natural variation of blood lipids, will be given for translation (i) of such technologies towards individualized lipidomic tracking and (ii) for better mechanistic understanding of lipid function.