Sankha (Bobby) Basu, MD, PhD received his BS in Biology and Chemical Engineering in 2003 at MIT and obtained his MD and PhD (Pharmacology) degrees in 2013 from the University of Pennsylvania School of Medicine. His thesis work involved the development and application of stable isotope LC-MS/MS methods to study mitochondrial disease, which was conducted in the laboratory of Dr. Ian Blair. He then went back to Boston to complete a residency in Clinical Pathology and a fellowship in Medical Microbiology at the Brigham and Women's Hospital (BWH). Following his clinical training, he joined the laboratory of Dr. Nathalie Agar at BWH as a post-doctoral research fellow working on a variety of applications including intraoperative MS and MALDI MSI. He recently joined the faculty at BWH as Assistant Director of Clinical Chemistry and Mass Spectrometry and Instructor of Pathology at Harvard Medical School. His clinical roles include the development and implementation of LC-MS methods in clinical chemistry and MALDI TOF based microbial identification in microbiology. Additionally, he continues his work with the Agar lab on clinical and translational applications of MS.

Christina R. Ferreira works as Lipidomics Scientist in the Metabolite Profiling Facility at Purdue University. Her main research interest is the application of the MRM-profiling method for the exploratory analysis of lipids and metabolites in developmental biology models. At Prof. Cooks lab, she created the MRM-profiling method and contributes to diverse projects from the Cooks lab related to further developing this method. Dr. Ferreira also supports the application MRM-profiling in research projects served by the multi-user Purdue Metabolite Profiling Facility at Bindley Bioscience Center. She is also the project manager for a large effort (Purdue Make-It System) for high-throughput screening and analysis of chemical reactions using DESI-MS.

Michelle Reyzer received her BS in Chemistry from the College of William and Mary in Virginia in 1991, and after that worked at the NIH at the National Institute for Alcohol Abuse and Alcoholism (NIAAA) in the Laboratory of Membrane Biochemistry and Biophysics for 5 years. She then went to the University of Texas at Austin where she received a PhD in Analytical Chemistry in 2000 in the laboratory of Jennifer Brodbelt. The was followed by a post-doctoral fellowship at Vanderbilt in the laboratory of Richard Caprioli where she was introduced to MALDI Imaging Mass Spectrometry. She has been focused on the use of MALDI for imaging biological tissues for the past 14 years. Michelle is currently a Research Assistant Professor at Vanderbilt University Medical Center, and also serves as the Associate Director of the Tissue Imaging Core laboratory, where she routinely develops methods for the analysis of small molecules in tissue sections for investigators within Vanderbilt as well as external collaborators. In addition, Michelle oversees the collaboration and service projects for the National Research Resource for Imaging Mass Spectrometry.

This is a 2-Day Course with 7 total contact hours.

Overview: Over the past two decades we have seen considerable scientific and technological advancements in imaging mass spectrometry (IMS), as these approaches continue to be implemented in research and industry. There has, however, been limited adoption of these techniques into the clinical arena, in part due to gaps between the mass spectrometrists developing these tools, and the clinical stakeholders, such as surgeons and pathologists, who may one day use them in their practices.

The goal of this course is to bridge these gaps by (1) providing an overview of the principles, strengths, limitations and applications of IMS techniques, such as MALDI-IMS and ambient mass spectrometry (AMS), and (2) offering insight into clinical workflows and potential opportunities for applications. The target audiences include both clinicians, surgeons, and pathologists interested in learning more about IMS applications as well as mass spectrometrists interested in clinical applications of IMS. The first day will focus on MALDI IMS, while the second day will cover ambient MS.

Thursday

7:00 - 8:10am
Clinical tissue analysis: overview of workflows and diagnostic "blind spots" (BB) (70 min)

8:20 - 9:30am
Introduction to MALDI IMS (MR) (70 min)

9:40-10:50am
Advancements and applications using MALDI IMS (MR) (70 min)

Friday

7:00 - 8:10am
Introduction to ambient MS (CF) (70 min)

8:20 - 9:30am
Advancements and applications using AMS (CF) (70 min)

9:40-10:50am
Bringing IMS into the clinic: opportunities and challenges (BB) (70 min)

Grace is an LC-MS/MS Applications Development Specialist at St Paul’s Hospital in Vancouver BC. She is passionate about developing the most user friendly and streamlined LC-MS/MS assays as possible for routine use in the Special Chemistry Mass Spec Lab. She loves troubleshooting, especially when the cause of problem has been discovered and the issue solved!

Deborah French Ph.D., DABCC (CC, TC) is currently Assistant Director of Chemistry and Director of Mass Spectrometry at the University of California San Francisco Clinical Laboratories. Her work currently focuses on the development and validation of LC-MS/MS assays for small molecules, specifically therapeutic drug monitoring, steroid hormones and toxicology. Deborah received her Ph.D. in biochemistry from the University of Strathclyde in Glasgow, Scotland and then completed a postdoctoral fellowship at St. Jude Children’s Research Hospital in Memphis, TN. She subsequently completed a ComACC Clinical Chemistry postdoctoral fellowship under the direction of Dr Alan Wu at the University of California San Francisco and is now board certified in Clinical Chemistry and Toxicological Chemistry by the American Board of Clinical Chemistry.

Lorin Bachmann joined the VCU Department of Pathology in 2007. She currently serves as Co-Director of Clinical Chemistry, Co-Director of Point-of-Care Testing, Director of the New Kent Emergency Department Laboratory, Technical Advisor for the Operating Room Laboratory, Pathology Outreach and Clinical Trials, and Laboratory Director for multiple VCUHS outreach laboratories. Dr. Bachmann received her PhD in Molecular Medicine from the University of Virginia, followed by a fellowship in clinical chemistry and proteomics research at the University of Virginia. Dr. Bachmann is certified by the American Board of Clinical Chemistry.

Dr. Bachmann is active within the American Association for Clinical Chemistry (AACC), where she serves on the Board of Directors. She also serves as the Chair of the Chemistry and Toxicology Expert Panel for the Clinical Laboratory and Standards Institute (CLSI).

Dr. Bachmann’s research interests include evaluation and validation of new clinical laboratory assays, clinical laboratory analyzer design, development of mass spectrometry-based assays for the clinical laboratory and standardization of laboratory testing. She serves as the Chair of the National Kidney Disease Education Program (NKDEP)/International Federation of Clinical Chemistry Laboratory (IFCC) Joint Lab Working Group, whose goal is to accomplish standardization of urine albumin methods to enable utility of clinical decision thresholds.

Dr. Bachmann has received numerous awards for her contributions to professional societies, education and research. She serves as principal investigator for multiple industry-sponsored studies.

This is a VIRTUAL 4-Day Course with 16 total contact hours. CE to be provided.

Online Format

This is a virtual version of the short course that has been presented at MSACL. This online course includes 2.5-5 hours of live lecture each day for four days. Using Zoom (live online lectures, breakout rooms for interactive sessions) and Google Classroom (forms and job aids for download, on demand short lecture videos) provides additional opportunities for interactive and self-paced learning, both during the four-day course and beyond.

The resources posted in Google Classroom will be available to registrants for at least 3 months. We can’t give you hands-on experience with cutting PEEK tubing or changing check valves in an online course. But the potential with a virtual platform for networking and updates with actionable information to help you with your daily LC-MS/MS clinical practice seems almost limitless.

Course Content Description

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:

1. LC-MS/MS system purchasing
2. site preparation and installation
3. defining preliminary MSMS and LC parameters for your first method
4. selecting and optimizing sample preparation for your first method
5. choosing internal standards, solvents, and water, making reagents and calibrators
6. adjusting sample preparation, LC and MSMS parameters to achieve the desired assay performance
7. establishing data analysis & batch review criteria
8. pre-validation stress testing and method validation
9. preventative maintenance and troubleshooting
10. 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. The IFCC Committee for Distance Learning published a curriculum guideline for post-graduate trainees in laboratory medicine in 2017. This course includes all of the IFCC mass spectrometry curriculum listed in the “Principles of Analysis X-MS” section, except that we focus only on triple quadrupole mass spectrometry; metabolomics, proteomics and inborn errors of metabolism are not discussed. See also this reference by one of the team of short course instructors “Liquid chromatography-mass spectrometry education for clinical laboratory scientists”.

Previous exposure to the principles of clinical method validation, either didactic or practical, is assumed. A post-course online exam will be available, with a certificate of completion for those who take and pass the exam within the examination window of two weeks after the four day short course.

Professor Jack Henion is Emeritus Professor of Toxicology at Cornell University where he was a member of the College of Veterinary Medicine commencing in 1976. Dr. Henion was co-founder of Advion BioSciences in 1993 where he served as President and CEO until 2006 when be became CSO of Advion, Inc. Dr. Henion carried out a wide range of research in many application areas involving GC/MS and LC/MS/MS techniques. Professor Henion has received three Doctor Honoris Causa (Honorary Doctorate) degrees in recognition of his international reputation in modern analytical techniques. These were awarded from each of the University of Ghent, Uppsala University and Albany University. During his tenure at Cornell Professor Henion conducted research and explored applications in many areas of liquid chromatography/mass spectrometry (LC/MS) employing atmospheric pressure ionization (API) sources. Professor Henion has published over 235 peer reviewed papers in the scientific literature, trained nearly 100 students, post-doctoral scientists, and trainees while receiving 12 patents for inventions developed from his work. He has also received a number of awards which recognize his contributions to analytical chemistry and entrepreneurship. More recently in April 2017 Dr. Henion received the Outstanding Contribution to Anti-Doping Science Award from the Partnership for Clean Competition (PCC) for his development of a novel Book-Type Dried Plasma Spot Card and in the Fall of 2017 Dr. Henion was the winner of the 2018 Bioanalysis Outstanding Contribution Award (BOSCA). In December 2019 Dr. Henion retired from Advion, Inc. and is now a consultant for Henion Enterprises.

This course presents presents a comprehensive overview of technology and techniques of analytical mass spectrometry and from that foundation extends into exciting, disruptive recent developments.

1. Sample preparation




• Topics: New types of extraction, Issues to consider, Isolation of proteins from biological samples Ultrafiltration, Affinity techniques, Molecularly Imprinted Polymers (MIP?s), Aptamers, Thermo's MSIA pipette tips, Electro Extraction, Quechers, SISCAPA, Micro extractions: Dried blood spots (DBS), Dried Plasma Spots (DPS).
  


2. Advanced separation techniques for large molecules




• Topics: UHPLC, Hydrophobic Interaction Chromatography (HIC), Nano-UHPLC, Micro LC/MS, Size Exclusion Chromatography (SEC), ion exchange chromatography, Capillary Electrophoresis (CE), Differential Mobility Spectrometry (DMS).
  




3. Ionization techniques for MS




• Topics: Electrospray ionization (ESI), Nano ESI, Micro ESI, Atmospheric pressure chemical ionization (APCI), Atmospheric pressure photoionization (APPI), Matrix assisted laser desorption ionization (MALDI), LAESI, Electron Ionization (EI) and its potential for LC/MS.
  


• 
  To Discuss: New ionization techniques which may be used without on-line separation science technology. This area has evolved into a variety of ambient ionization techniques such as DESI, DART, ASAP, etc.
  





4. Mass Analyzers




• Quadrupoles, Ion traps, linear and quadrupole, Time-of-Flight (TOF), Orbitraps, Hybrid mass analyzer systems, Ion mobility spectrometers, and Differential Mobility Spectrometry (DMS).
  


• 
  To Discuss: Developments and improvements in mass analyzers including linear ion traps, FTMS, time-of-flight (TOF), orbitraps, and accelerator mass spectrometry (AMS), the latter currently being applied to micro-dosing experiments by the pharmaceutical industry. Issues such as full-scan acquisition rates, high-resolution mass spectrometry (HRMS), the importance and usefulness of exact mass measurements for qualitative and quantitative analysis, and the analytical merits compared with modern SRM LC/MS experiments will be discussed with many practical examples and applications. The latter will include clinical chemistry issues as well as pharmaceutical, food safety, environmental and industrial examples.
  




5. Imaging and profiling by MS




• Applications of recently reported ionization techniques for imaging the location of chemicals in various matrices employing MALDI, DESI, LAESI, LESA and other techniques.


• 
  Topics: The technique of MALDI and its applications to tissue imaging as well as DESI, LAESI and also liquid extraction surface analysis (LESA) employing nano-electrospray. A comparison of the various classes of compounds where MALDI and nano ESI provide complimentary coverage of certain compounds found in biological and other matrices.
  




6. High resolution MS




• Topics: Fundamentals, Mass Defects, Isotopic patterns, Mass axis calibration, Types of HRMS systems, Qual/Quan Analysis, Data mining processes, Future directions
  


• To Discuss: The analytical merits of HRAMS from QTOF as well as orbitraps and FTMS systems will be presented. Instances where either SRM LC/MS or LC HRAMS may be preferred for optimal selectivity due to chemical background or other interference issues.
  




7. Miniaturization in MS




• Topics: Purdue University "Mini 11", Torion, Microsaic, Advion expression CMS, Waters QDa
  


• 
  To Discuss: The benefits and limitations of smaller analytical instrumentation systems will be compared. This includes miniaturization of HPLC systems as well as the mass spectrometers themselves. The commercial introduction of chip-based HPLC systems closely integrated with mass spectrometers offers a glimpse of future directions in analytical chemistry.
  




8. Synergistic Integration




• A systematic overview via specific examples with applications highlighting noted examples of innovative novel and non-standard technologies which demonstrate the analytical potential of new analytical technologies.
  


• 
  Developing instrumentation and technologies will be important aspects of future mass spectrometry techniques and its expansion to important new applications. An extremely important example is the need for LC/MS bioanalysis (quantitation) of biologics (ADC?s, large molecules, RNA, etc.) in biological samples employing both bottom up and top down methods. HRAMS coupled with „protein friendly? chromatography will significantly expand our present analytical capabilities. Ion mobility spectrometry (IMS) and transportable mass spectrometers could lead to point-of-care applications and other far reaching applications of mass spectrometry beyond what we are doing today. The future is very exciting!
  

Patrick Mathias, M.D., Ph.D., is a board-certified clinical pathologist and Associate Director of Informatics for UW Laboratory Medicine.

Lab medicine has large impact on the general practice of medicine. It is key to correctly diagnosing diseases and selecting the right treatments for patients. Dr. Mathias's goal is to combine technical and medical knowledge to fulfill the triple aim--reduce the per capita cost of health care, improve the health of populations and most importantly improve the patient experience of care.

Dr. Mathias earned his M.D. and Ph.D. from the University of Illinois. His clinical and research interests include clinical informatics, clinical chemistry and molecular diagnostics.

My lab performs research and clinical testing using mass spectrometry methods, develops new assays, and applies data analytics to enable improved quality and efficiency. My computational pathology efforts are aimed at building the capacity for advanced data analytics in the department through innovations in infrastructure, education, and research to facilitate data-informed decision making for clinical care, operations, and quality assurance.

This is a VIRTUAL 4-Day Course with 16 total contact hours. CE to be provided.


Overview:

Having completed your first steps into the wonderful world of data analysis with R, would you like to go further? You’ve learned the basics of R, so now it’s time to put that knowledge to work and tackle some interesting clinical applications. Along the way you will also be introduced to even more of capabilities of R and the tools developed by the amazing R community.

The 4-DAY ONLINE ONLY virtual (via Zoom) short course will be split between lecture sessions, individual problem solving, and a highly interactive group-level data mining of real data sets. Like the introductory course, this class will maintain the “no student left behind policy”. Students will be given time to solve problems taken from real-life laboratory work and to do some more advanced analysis on large scale data sets. All attendees will need access to a laptop with both R language and R Studio interface installed. Students may use Windows, Mac OSX or Linux environments. Both R and R studio are free and open-source.

Students should be prepared to continue to expand their skill in programming – which, as you learned in the introductory course (Data Science 101) can be a little frustrating, but not as frustrating as not being able to get the computer to do what you want at all!

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:

1. Core concepts in reproducible research
2. Introduction to R-Markdown for report generation
3. Conceptual basis for keeping data “tidy”
4. Using the Import -> Tidy -> Transform -> Visualize -> Model -> Communicate pipeline
5. Data wrangling and manipulation operations such as filtering, grouping, summarizing
6. Data exploration and visualization with the ggplot2 library
7. Prediction with linear regression and classification with logistic regression
8. Database basics & connecting to databases
9. Putting it all together project: analysis of large mass spectrometry data set using exploratory data analysis

Course material will be provided electronically.

Guinevere received her PhD on exploring prostate-specific antigen (PSA), the well-known biomarker for prostate cancer, and its glycosylation by capillary electrophoresis and mass spectrometry. Currently, Guinevere performs her post-doctoral research at the Center for Proteomics and Metabolomics at the Leiden University Medical Center, in the group of prof. Manfred Wuhrer. She currently works on further expanding a mass spectrometry-based PSA glycosylation assay which she developed during her PhD. In addition, she explores the possibilities for the in-depth analysis of glycans and intact glycoproteins for biomarker discovery for other diseases as well as for the characterization of biopharmaceuticals. In 2017, Guinevere joined the organization committee of the Netherlands Area Biotech (NLab) Discussion group of CASSS. In 2019, she became a member of the scientific committee of the glycomics session, and a member of the early career committee, of MSACL EU. Her research interests are focused on bringing together researchers from the field of biomarker discovery with clinical laboratory professionals, ensuring a better translation of potential biomarkers to the clinic. Moreover, she is dedicated to convincing her fellow colleagues that glycosylation is an important subject and should not be neglected just because it is rather complicated.

Noortje is conducting her post-doctoral research at the Center for Proteomics and Metabolomics at the Leiden University Medical Center, The Netherlands. She obtained her MSc degree in Pharmaceutical Sciences at the VU University Amsterdam, The Netherlands, with a focus on biomarker research and clinical chemical analysis. She received her PhD at the Leiden University Medical Center, under the supervision of prof. Manfred Wuhrer, on the development and application of various mass spectrometry-based methods for the analysis of (antibody) glycosylation. Noortje’s enthusiasm for glycoproteomic-related research started early in her scientific career and this remains a key drive in her current work. She is interested in the development of mass spectrometric methods and data analysis protocols for addressing clinical research questions.

Did you ever encounter glycans, but you -kind of- neglected them as they seemed too complicated to characterize? Or did you just perform a glycan release to make the analysis of your protein a lot easier? Do you have no idea how to interpret your data when a glycan is present? Fear no more! We are here to provide you with the basics in the field of mass spectrometric glycomics and glycoproteomics.

The course will start with a historical overview on glycan research (i.e. how did glycans work their way up to being acknowledged as important study objects) and we will guide you through the maze of different nomenclatures. Moreover, although glycans are well known for their complexity, we will reveal to you the “rules of glycan structures” based on known biosynthetic pathways. This will be followed by an in-depth discussion on glyco(proteo)mic mass spectrometric technologies and workflows. In addition, different sample preparation steps will be covered. We will close-up with a session about glycomic biomarker discovery, as it can hardly be considered a coincidence that, for example, more than 80% of the currently used cancer biomarkers are glycosylated.

The course will run over 4 days and time will be split between lectures and workshops (e.g. how do you recognize a glycan in a mass spectrum and how do you assign it). While not everything can be covered within these 4 days we will ensure that you will know your “glyco-basics” in the end. Moreover, participants are encouraged to submit any specific glyco-questions they have prior to the course and we will try to discuss them during the course.

Brief outline of the course:

1. Historical overview of glycosylation research
2. Glycans from a chemical perspective
3. The biosynthetic pathway of N-glycans, O-glycan and glycosphingolipids
4. Biological function of glycans
5. Historical overview of glycoanalytics
6. How to analyze and interpret your glycan, glycopeptide and/or glycoprotein with mass spectrometry
7. Glycomic biomarker discovery - Finding the sweet spot of the disease

Guinevere received her PhD on exploring prostate-specific antigen (PSA), the well-known biomarker for prostate cancer, and its glycosylation by capillary electrophoresis and mass spectrometry. Currently, Guinevere performs her post-doctoral research at the Center for Proteomics and Metabolomics at the Leiden University Medical Center, in the group of prof. Manfred Wuhrer. She currently works on further expanding a mass spectrometry-based PSA glycosylation assay which she developed during her PhD. In addition, she explores the possibilities for the in-depth analysis of glycans and intact glycoproteins for biomarker discovery for other diseases as well as for the characterization of biopharmaceuticals. In 2017, Guinevere joined the organization committee of the Netherlands Area Biotech (NLab) Discussion group of CASSS. In 2019, she became a member of the scientific committee of the glycomics session, and a member of the early career committee, of MSACL EU. Her research interests are focused on bringing together researchers from the field of biomarker discovery with clinical laboratory professionals, ensuring a better translation of potential biomarkers to the clinic. Moreover, she is dedicated to convincing her fellow colleagues that glycosylation is an important subject and should not be neglected just because it is rather complicated.

Noortje is conducting her post-doctoral research at the Center for Proteomics and Metabolomics at the Leiden University Medical Center, The Netherlands. She obtained her MSc degree in Pharmaceutical Sciences at the VU University Amsterdam, The Netherlands, with a focus on biomarker research and clinical chemical analysis. She received her PhD at the Leiden University Medical Center, under the supervision of prof. Manfred Wuhrer, on the development and application of various mass spectrometry-based methods for the analysis of (antibody) glycosylation. Noortje’s enthusiasm for glycoproteomic-related research started early in her scientific career and this remains a key drive in her current work. She is interested in the development of mass spectrometric methods and data analysis protocols for addressing clinical research questions.

This is a continuation of the course from Part 1 and is not intended to be taken separately.

this isn't it

Randy Julian is CEO, President, and Founder of Indigo BioAutomation (originally, Indigo Biosystems) located in Indiana. Randy earned a Ph.D. in Chemistry from Purdue University in 1993 and then worked in Discovery Chemistry at Eli Lilly for 14 years. Randy founded Indigo based on informatics technology developed in his research group. Dr. Julian led Indigo from its founding to profitability, building a world class management, engineering and research team to commercialize laboratory data analysis software.

Dr. Julian is a frequent speaker in the mass spectrometry community and teaches short courses in statistics and data analysis. Randy is the past Chairman of the Human Proteome Organization’s Proteomics Standards Initiative Steering Group where he coauthored two international standards for analytical data. He was also the chairman of the ASTM committee on analytical data standards. Dr. Julian also maintains an active research relationship with the faculty at Purdue University where he is an Adjunct Professor of Chemistry.

Level: Intermediate
Prereqs: Data Science 101 or 201 (or equivalent experience)

Overview: Machine learning techniques have been highly successful in driving the growth of Amazon, Google, Netflix, and other companies that rely on identifying patterns in big data. More importantly, these algorithms are beginning to revolutionize clinical diagnosis and mass spectrometry, from FDA-approved retinal image analysis to robust detection of mass spec chromatographic peaks. But ... what exactly is machine learning? How does it work? How can you apply it to your own data? In this course, we will help you sort through the hype and provide an introduction to machine learning, including an overview of common approaches, known pitfalls, and other important concepts. We will include practical instruction on applying machine learning algorithms using the R statistical language, so familiarity with R at the level of the material taught in Data Science 101 and/or 201 is desirable.