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Short Courses

MSACL hosts a diverse offering of Short Courses.

Short Courses cover 1 to 2 days, depending on the course, for the first two days of the congress (Sept 12-13).

*Notes:

1. Two day courses are NOT the same courses replicated on two separate days. They are single courses that span two days.
2. Unless otherwise noted, courses are from approximately 09:00 - 18:00 (Monday) and 09:00 - 18:00 (Tuesday).

:: Data Science 101
Breaking up with Excel: A Newbie's Introduction to the R Statistical Programming Language
Daniel Holmes, MD & Stephen Master, MD PhD
Level: 1-2 (Beginner - Intermediate)
Length: 2 Days (Monday - Tuesday)
Location: Mozart 5

:: Lab Medicine 101
Basics of Laboratory Medicine
Prof. Dr. med. Michael Vogeser
Level: 1 (Beginner)
Length: 1 Day (Monday)
Location: Doppler

:: LC-MSMS 101
Getting Started with Quantitative LC-MS/MS in the Diagnostic Laboratory
Judy Stone, PhD & Grace van der Gugten
Level: 1-2 (Beginner - Intermediate)
Length: 2 days (Monday - Tuesday)
Location: Mozart 4

:: LC-MSMS 202
Practical LC-MS Maintenance and Troubleshooting
Erik J. Soderblom, PhD, J. Will Thompson, PhD
Level: 2 (Intermediate)
Length: 2 Days (Monday - Tuesday)
Location: Trakl

:: LC-MSMS 301
Development and Validation of Quantitative LC-MS/MS Assays for Use in Clinical Diagnostics
Russell Grant, PhD & Brian Rappold
Level: 3 (Advanced)
Length: 2 Days (Monday - Tuesday)
Location: Papageno Hall

:: Metabolomics 201
Metabolomics: Approaches, Applications and Challenges
Julijana Ivanisevic, PhD & Elizabeth Want, PhD
Level: 1-2 (Beginner to Intermediate)
Length: 1 Day (Tuesday)
Location: Doppler

:: Proteomic Microbiology 201
Bottom-Up and Top-Down Proteomic Approaches for Bacterial Identification and Characterization, a Focus on MALDI-TOF and Advanced Technologies
Jean-Armengaud, PhD, Dr. med. Irene Burckhardt, Stefan Zimmermann, MD
Level: 1-2 (Beginner - Intermediate)
Length: 1 Day (Tuesday)
Location: Trapp

:: Proteomics 201
Clinical Proteomics
Cory Bystrom, PhD & Chris Shuford, PhD
Level: 2-3 (Intermediate - Advanced)
Length: 2 Day (Monday - Tuesday)
Location: Paracelsus

:: Data Science 101
Breaking up with Excel: A Newbie's Introduction to the R Statistical Programming Language

Prerequisites:

• knowledge of Excel
• able to bring a laptop
• able to pre-install software on their laptop...Namely: R and R-studio
• willingness to break up with Excel

Overview: Have you ever tried to do Deming regression in Excel only to discover that it is not available? Have you had your figure rejected by a journal because the resolution was not good enough? Have you wished that you could figure out a way to stop manually transcribing your LC-MS/MS results into the LIS?

Well, your wait is over because this year at MSACL we will be offering a course for complete programming newbies that will help you get going analyzing real data related to LC-MS/MS assay development, validation, implementation and publication. The only background expected is the ability to use a spreadsheet program. The skills that you will acquire will allow you to take advantage of the many tools already available in the R language and thereafter, when you see that your spreadsheet program does not have the capabilities to do what you need, you will no longer have to burst into tears. You will be empowe-R-ed.

The course will be run over two days and time will be evenly split between didactic sessions and hands on problem solving with real data sets. Drs Holmes and Master will adopt a “no student left behind policy”. Students will be given ample time to solve mini problems taken from real life laboratory work and focused on common laboratory tasks. All attendees will need to bring a laptop with the R language installed R Studio interface installed. Students may use Windows, Mac OSX or Linux environments. Both R and R studio are free and open-source. No cash required.

Students should be prepared for learning what computer programming is really like. This may involve some personal frustration but it will be worth it.

Obtaining the Software

Instructions for installing the R language are here: http://cran.r-project.org/
Instructions for installing R Studio are here: http://www.rstudio.com/

Course Description

The course will cover:

• The major types of R variables: vectors (numerical, character, logical), matrices, data frames and lists.
• The important classes: numeric, character, list and changing between them
• Importing data from Excel
• Dealing with non-numeric instrument data: the “<10”s and “>1000”s.
• Manipulating your data: sub-setting, which, match, sort, unique, cut
• Simple statistical tests: mean, median, quantiles (normal ranges), t-tests, ANOVA, Wilcoxon.
• Data merges: matching rows between sets
• Exporting data to Excel-like format.
• Regressions: Ordinary Least Squares,Passing Bablok, Deming, weighted regressions.
• Non-linear regressions
• Looping: Doing things repeatedly
• Writing your own functions
• Making highly customized graphs: scatter plots, regression lines, histograms, box plots, qq-plots
• Putting it all together projects:
  • Preparing method comparison regression and Bland Altman plots
  • Preparing mass spectrometry data for upload to LIS.

Co-Instructor: Daniel Holmes, MD

Clinical Associate Professor, Department of Pathology and Laboratory Medicine, University of British Columbia

Daniel Holmes did his undergraduate degree in Chemical Physics from the University of Toronto with a focus on Quantum Mechanics. He went to medical school at the University of British Columbia (UBC) where he also did his residency in Medical Biochemistry. He is a Clinical Associate Professor of Pathology and Laboratory Medicine at UBC and Division Head of Clinical Chemistry at St. Paul's Hospital in Vancouver. Interests include laboratory medicine statistics, clinical endocrinology, clinical lipidology and clinical mass spectrometry. Assay development efforts in the last two years have focused on assays specialized endocrine testing.

Co-Instructor: Stephen Master, MD, PhD

Associate Professor of Pathology and Laboratory Medicine, Weill Cornell Medical College

Stephen Master received his undergraduate degree in Molecular Biology from Princeton University, and subsequently obtained his MD and PhD from the University of Pennsylvania School of Medicine. After residency in Clinical Pathology at Penn, he stayed on as a faculty member with a research focus in mass spectrometry-based proteomics as well as extensive course development experience in bioinformatics. He is currently Associate Professor of Pathology and Laboratory Medicine at Weill Cornell Medicine in New York City, where he serves as Director of the Central Lab and Chief of Clinical Chemistry Laboratory Services. One of his current interests is in the applications of bioinformatics and machine learning for the development of clinical laboratory assays. He would play with R for fun even if he weren't getting paid, but he would appreciate it if you didn't tell that to his department chair.

:: Lab Medicine 101
Basics of Laboratory Medicine

Prerequisites:

Overview: This 1-day course aims to make scientists familiar with the basic concepts of clinical pathology and laboratory medicine. Typical processes and workflows in the various categories of clinical laboratories are described and discussed. Topics that are addressed include in particular:

- Basic technologies (photometry, immunoassays, electrochemical methods, cytometry, immuno-fluorescence, etc.)

- Automation and working characteristics of analyzer configurations including total laboratory automation Concept of total testing process including pre- and post-analytical processes

- Performance characteristics

- Quality management

- Regulatory background

- Sample materials

- Clinical decision making, reference ranges, decision levels, diagnostic and clinical algorithms

- Logistics, sample transport

- Economic considerations

- Characteristics of IVD industry

Dr. Michael Vogeser, MD, is specialist in Laboratory Medicine and senior physician at the Hospital of the University of the Ludwig-Maximilians-University Munich, Germany (Institute of Laboratory Medicine). As an Associate Professor he is teaching Clinical Chemistry and Laboratory Medicine.The main scope of his scientific work isthe application of mass spectrometric technologies in routine clinical laboratory testing as translational diagnostics. Besides method development in therapeutic drug monitoring and endocrinology a further particular field of his work isquality and risk management in mass spectrometry and in clinical testing in general.Michael has published >150 articles in peer reviewed medical journals and is secretary of the German Association of Clinical Chemistry and Laboratory Medicine (DGKL) (2016 – 2019).

:: LC-MSMS 101
Getting Started with Quantitative LC-MS/MS in the Diagnostic Laboratory

Prerequisites:

Overview: Is your laboratory under pressure to purchase an LC-tandem MS or is the ROI you wrote last year haunting you now? This short course is designed for attendees implementing quantitative LC-tandem MS for patient testing who have laboratory medicine experience but no mass spectrometry training - CLS bench analysts, supervisors, R&D scientists, and laboratory directors. Theoretical concepts necessary for a robust implementation of clinical mass spectrometry will be presented – but the emphasis is on practical recommendations for:

• LC-MS/MS system purchasing
• site preparation and installation
• defining preliminary MSMS and LC parameters for your first method
• selecting and optimizing sample preparation for your first method
• choosing internal standards, solvents, and water, making reagents and calibrators
• adjusting sample preparation, LC and MSMS parameters to achieve the desired assay performance
• establishing data analysis & review criteria and an interface to the LIS
• pre-validation stress testing and method validation
• preventative maintenance and troubleshooting
• maintaining quality in production.

Our goal is to present just enough theory so you can report high quality results, while opening a window to the depth and complexity of clinical mass spectrometry such that your appetite is whetted to learn more.

Previous exposure to the principles of clinical method validation, either didactic or practical, is assumed. A glossary of common LC-MSMS terms/acronyms, and diagrams delineating basic LC and MSMS instrument components and functions will be emailed to attendees a week prior to the beginning of the course. This material will also be addressed at the beginning of the course, but the initial learning curve can be steep and review prior to the course will be beneficial if you have absolutely no previous exposure with LC-MSMS.

:: LC-MSMS 202
Practical LC-MS Maintenance and Troubleshooting

Prerequisites: Experience with LC-MS systems.

Overview: The general goal of the course is to enable practitioners of LC-MS/MS in the clinical laboratory to quickly recognize and diagnose specific problems with instrumentation, in order to decrease downtime and cost of repairs. The course includes ‘best practices’ for instrumentation installation, upkeep and maintenance, practical troubleshooting workflows for LC and MS, and will use problem sessions to reinforce skillsets. Although the course uses examples from specific instrumentation for demonstration, the content is geared to be vendor-neutral and applicable to all LC-MS systems. Additionally, we will provide an opportunity to have instrumentation troubleshooting questions from your laboratory addressed by the facilitators.

Brief outline of course content:

• General “Best Practices” for Successful LC/MS Operation
  1. Best Practices; Getting Started on the Right Foot
  2. Breaking the System Down
  3. System Suitability! What is it, and how do I properly implement?
• Focus on Liquid Chromatography
  1. Diagnostics using the “heartbeat” of your Chromatographic system
  2. Key System components and where things go wrong
  3. LC troubleshooting workflow
  4. Maintenance Intervals; service contract or do-it-yourself?
  5. Problem sets
• Focus on Mass Spectrometry
  1. Discussion of Source, Transfer Optics, Vacuum and how each is critical to your system
  2. MS Troubleshooting workflow
  3. Ion optics cleaning and upkeep; what is ‘charging’?
  4. Problem sets
• Integrated System
  1. Ionization
  2. System Communications
  3. Multi-vendor configurations
  4. Strategies to simplify
  5. Integrated real-lab problem scenarios and team exercises

While some basics of instrument component operation will be covered, it will be most beneficial to scientists with experience actively using LC-MS/MS as an analysis tool. While an in-depth discussion of how to operate each individual instrument is surely outside the scope of any short course, specific system setups will be used as examples and attendees will be encouraged to ask questions about specific systems in their own laboratories.

Co-Instructor: Will Thompson, PhD

Dr. Thompson received his Ph.D. in Analytical Chemistry from the University of North Carolina at Chapel Hill under Professor James Jorgenson in 2006. Following his Ph.D. he pursued a career in the application of UHPLC with high resolution mass spectrometry in the Disease and Biomarker Proteomics group of Dr. Arthur Moseley at GlaxoSmithKline, leaving GSK in 2008 to join Dr. Moseley in establishing the Duke Proteomics Core Facility. Dr. Thompson is currently the Assistant Director of the Duke Proteomics and Metabolomics Shared Resource, and a Research Assistant Professor in Department of Pharmacology and Cancer Biology. His research interests involve improving the throughput and sensitivity of unbiased and targeted proteomics and metabolomics approaches, with an eye towards generating assays which are easily translatable to the diagnostic laboratory. Co-Instructor: Erik J. Soderblom, PhD

Dr. Erik Soderblom currently holds a joint appointment as a Research Scientist at Duke University’s Proteomics and Metabolomics Core Facility and as an Assistant Research Professor in Duke University’s Department of Cell Biology. He received a PhD in Molecular and Structural Biochemistry from North Carolina State University in 2008, prior to joining the Core Facility. His expertise lies in the utilization of various liquid chromatography-mass spectrometry (LC-MS) platforms to support a wide variety of research efforts from small scale basic science studies to larger scale clinical proteomics studies. Dr. Soderblom has over 10 years’ experience in differential expression proteomics using single and multi-dimensional nanoscale capillary chromatography coupled to high-resolution mass spectrometers, targeted proteomic analysis using triple quadrupole mass spectrometers (MRM) or high-resolution mass spectrometers (PRM), and comprehensive analysis of post-translational modifications such as phosphorylation and acetylation. As part of his normal responsibilities, Dr. Soderblom is involved in routine maintenance and troubleshooting of both LC and MS components across various instrument platforms, including design and execution of system suitability analysis to assess platform performance over time.

:: LC-MSMS 301
Development and Validation of Quantitative LC-MS/MS Assays for Use in Clinical Diagnostics

Prerequisites: The target audience should have extensive familiarity with LC-MS/MS systems.

Overview: This 2-day course will briefly introduce the key aspects of the LC-MS/MS experimental workflow and then focus on processes and experimental designs for assay development and analytical validation of assays to be employed within clinical diagnostics.

The first day will describe method development in detail, including how-to guides for initial optimization of mass spectrometry systems, chromatographic development and sample preparation schemes. Techniques and technologies for streamlining analytical performance will also be described. Transitional experiments from development to validation will be discussed in detail to stress test methodologies prior to analytical validation.

Day two will cover all details pertinent in validation of LC-MS/MS analytical workflows. Experimental designs for all aspects of validation, putative acceptance criteria and analytical solutions will be shown. Key validation criteria of selectivity, carry-over, matrix effect, accuracy, precision, linearity, stability and inter-assay correlation will be described using multiple case studies.

Co-Instructor: Russell Grant, PhD

Dr. Grant received his PhD in chromatographic and mass spectrometric technologies from Swansea University in 1995. He continued his scientific training in various industrial settings which have included: senior scientist at GSK, principal scientist at Cohesive Technologies, Technical Director at Eli Lilly and Director of Mass Spectrometry at Esoterix Endocrinology.

Dr. Grant has pioneered the use of direct injection technologies, chromatographic systems multiplexing, utility of automation and new analytical platforms for application in bioanalytical applications. His research goals are focused upon improvements in speed, sensitivity and quality of LC-MS/MS analytical systems and assays.

Co-Instructor: Brian Rappold

Brian Rappold is the Scientific Director at Essential Testing in Collinsville, Illinois. He is a renowned expert in the field of method development and validation of mass spectrometry assays for clinical diagnostic use, teaching courses on this subject at numerous scientific conferences. His extensive knowledge and clinical perspective has granted him several opportunities to present his research internationally on the topics of hydrophilic interaction liquid chromatography for bio-analysis, multiplexed mass spectrometric detection of amino acidopathies and the origins and solutions of ion suppression in electrospray ionization. He currently serves as the chair of Clinical Chemistry for the American Society for Mass Spectrometry (ASMS) and has served on the Metabolomics and Small Molecule Analysis/Toxicology Scientific Committee for The Association for Mass Spectrometry: Applications to the Clinical Laboratory (MSACL). His research interests include the realization of open-access mass spectrometric systems and antibody-capture/mass spectrometry applications to diagnostic medicine.

:: Metabolomics 201
Metabolomics: Approaches, Applications and Challenges

Prerequisites:

Overview:

Metabolome: Downstream of Genome

• Central Dogma of Molecular Biology – From Genotype to Metabotype
• Historical Perspective of Metabolomics
• Technological platforms (NMR, GC/MS, LC/MS) and Applications
• OmicChallenge – Metabolite Diversity

Approaches in Metabolomics

• Targeted versus Untargeted (work on the front end vs. work on the back end, instrumentation, etc.)
• Experimental Design and Sample Preparation (depending on the approach)
• Choice of Analytical Platform (depending on the approach and metabolites of interest)
• OmicChallenge – « Big » Data Reduction

Data (Pre)Processing in Untargeted Experiments

• Step by step from peak picking to peak grouping and annotation
• Open-access platforms
• Hands-on XCMS Online
• Omic Challenge – Metabolite Identification

Statistical Analysis, Metabolite Identification and Mapping onto Pathways

• Univariateversus Multivariate Statistics (SIMCA, MetaboAnalyst)
• Metabolite Matching against Metabolite Databases (METLIN, HMDB, LIPIDMAPS, MassBank)
• Metabolite Set Enrichement Analysis and Network Modeling (MetaboAnalyst, KEGG, BioCyc, Mummichog, Ingenuity)
• Omic Challenge – Integration with other Omic Technologies in a Biologically Relevant Context

Co-Instructor: Julijana Ivanisevic, PhD

Julijana Ivanisevic is the head of the Metabolomics Research Platform (Senior Lecturer) at the Faculty of Biology and Medicine, University of Lausanne. Her research expertise is in mass spec­trometry-based metabolomics applications to biomedical research (brain metabolism, ageing, cancer metabolism), evolutionary biology and ecology. Her postdoctoral research was at the Center for Metabolomics at The Scripps Research Institute in La Jolla, California, USA.

Co-Instructor: Elizabeth Want, PhD

Elizabeth Want is a Senior Lecturer in Molecular Spectroscopy in the Department of Surgery and Cancer at Imperial College, London and the Director of the Imperial International Phenome Training Centre. She joined Imperial College in 2006 after working as a postdoctoral researcher at the Scripps Research Institute in La Jolla, CA. Her research at Imperial College involves the development, optimisation and application of LC-MS methodologies for the analysis of biological samples, largely in the context of metabolic phenotyping. She applies these methods to biomedical research areas including toxicology, cardiovascular disease, neonatal disease and development, and neurological diseases.

:: Proteomic Microbiology 201
Bottom-Up and Top-Down Proteomic Approaches for Bacterial Identification and Characterization, a Focus on MALDI-TOF and Advanced Technologies

Prerequisites:

Overview: This course will present an overview of bottom-up and top-down techniques for microbial identification using mass spectrometry-based technologies as well as their use in determination of microbial characteristics such as antibiotic resistance profiles. Topics to be discussed include:

• Comparison of bottom-up versus top-down proteomic approaches,
• Why top down proteomics is well-suited for microbial identification and characterization,
• Discrimination of closely related strains by top-down proteomics approaches.,
• Collection and interpretation of MALDI-TOF data,
• Proteogenomics as a means for improving annotations based on genomic sequence analysis and its use in identification of key protein markers in MALDI-TOF spectra.
• The concept of proteoforms as a means of categorizing the PTM states of proteins.
• The application of these techniques and technologies to antibiotic resistance determination,
• Novel methodologies that are currently emerging for the analysis of difficult samples, such as mixtures of pathogens and spores present within complex matrices.
• Recent advances for pathogen quantitation by tandem mass spectrometry.
• Use of MALDI-TOF for identification of viruses, molds and parasites.

Co-Instructor: Jean Armengaud, PhD
Jean Armengaud is best known for his work on proteogenomics of bacteria and the characterization of pathogens and radiotolerant organisms. He directs a mass spectrometry research unit located near Avignon in France that is dedicated to proteomics-based identification and quantitation of pathogens and environmentally relevant bacteria.

Co-Instructor: Dr. med. Irene Burckhardt

Co-Instructor: Stefan Zimmermann, PhD

:: Proteomics 201
Clinical Proteomics

Prerequisites: Practical knowledge of quantitative mass spectrometry.

Overview: This course will explore the background of clinical proteomics and approaches to method development and validation. We will provide the motivation for using mass spectrometry to quantify proteins in clinical research and in clinical care. The promise of mass spectrometry to improve the accuracy and precision of results is only realized with robust methods. In order to prepare participants to begin to develop their own robust methods for quantification we will focus on the following topics:

• Why mass spec for peptides and proteins
• Optimization of digestion and other aspects of the method
• Internal standards
• Calibration
• Peptide enrichment
• Validation
• Quality control
• Case studies

Co-Instructor: Cory Bystrom, PhD

Dr. Cory Bystrom serves as Director of Research and Development at Cleveland HeartLab where he is responsible for novel biomarker identification, validation and commercialization with an emphasis on quantitative biological mass spectrometry. Dr. Bystrom has over a decade of experience as a laboratory leader and chemist. Prior to joining CHL, he was at Quest Diagnostics Nichols Institute as associate director of research and development with responsibilities for development of tests and identification of analytical strategies for commercialization of new biomarkers. He also has held research and development roles at Oregon Health Science University, Fonterra, and Pharmacia and Upjohn.

Co-Instructor: Christopher Shuford, PhD

Chris Shuford, Ph.D., is Technical Director for research and development at LabCorp’s Center for Esoteric Testing in Burlington, North Carolina. Chris received his B.S. in Chemistry & Physics at Longwood University and obtained his Ph.D. in Bioanalytical Chemistry from North Carolina State University under the tutelage of Professor David Muddiman, where his research focused on applications of nano-flow chromatography (<500 nL/min) for multiplexed peptide quantification using protein cleavage coupled with isotope dilution mass spectrometry (PC-IDMS). In 2012, Chris joined LabCorp’s research and development team where his efforts have focused on development of high-flow chromatographic methods (>1 mL/min) for multiplexed and single protein assays for clinical application.