MSACL 2022 Program

MSACL 2022 : Program

Monterey, CA • April 5-8, 2022

2022 Sponsors

Abstract Clinical Use Status Key
= Emerging. More than 5 years before clinical availability. (19.79%)
= Expected to be clinically available in 1 to 4 years. (37.97%)
= Clinically available now. (42.25%)


Monday

Monday
1600
1900
Early Badge Pickup
@ De Anza Foyer
1888
Monday
1600
2000
Welcome Hospitality Reception
@ Jacks

Inside of Jacks Club Room

Drinks and very light snacks, not intended as a dinner substitute.

1889

Tuesday

Tuesday
630
Registration Desk Opens
@ De Anza Foyer
1906
Tuesday
800
1600
Vendor Booth Set-Up
@ Exhibit Hall - Serra
1962
Tuesday
800
1200
Workshop: A Clinical Proteomics Primer
@ De Anza 1

Andy Hoofnagle, MD, PhD
University of Washington

Christopher Shuford, Ph.D.
Labcorp


Objective

To provide an interactive forum in which attendees will be introduced to critical aspects of clinical protein measurements.

Summary

The motivation for using mass spectrometry to quantify proteins in clinical research and in clinical care will be discussed as part of this interactive workshop. Technical topics uniquely affecting quantitative protein and peptides measurements by mass spectrometry will be a point of emphasis. Case studies from assay inception through validation will be presented and participants will work interactively to critique various aspects of clinical proteomic measurements.

Syllabus
- Protein vs Peptide Measurands
- Workflows
- Sample Preparation (Digestion & Enrichment)
- Internal standards
- Calibration
- Validation
- Quality control

1853
Tuesday
800
1200
Workshop: Why We Fail at Biomarkers
@ De Anza 3

Tim Garrett, PhD
University of Florida College of Medicine


Objective

This workshop is designed to teach attendees reasons why most biomarkers do not translate to clinical diagnostics as a way to improve the process for future research

Summary

Biomarker discovery is one of the major areas of clinical research especially in metabolomics yet less than 1% of published biomarkers translate to clinical diagnostics. Biomarker discovery generally starts in phase 1 with a few samples to identify a biomolecule that differentiates the disease or disorder under investigation from control samples. Once a biomolecule is selected a targeted quantitative method would be developed in phase 2 to use on a larger number of samples to validate the results from phase 1. There are several common reasons for biomarker failure such as using samples that are not representative of the clinical population, not including diversity in the initial discovery phase, improper use of statistical approaches, not having a sufficient number of samples and improper quality control for analysis. With the growth of metabolomic methods recently, a discussion on approaches to help improve phase 1 of biomarker discovery is important to have confidence that the selected markers are indeed unique.

Syllabus

- Metabolomics in clinical research
- Quality control for better method assessment
- Experimental design
- Statistical analyses with validation
- Real-world samples

1897
Tuesday
800
1200
Short Course: Data Science 101 : Breaking up with Excel: An Introduction to the R Statistical Programming Language
@ Bonsai

Daniel Holmes, MD, FRCPC
St. Paul’s Hospital

Dustin Bunch, PhD, DABCC
Nationwide Children's Hospital


** Part In-Person (optional, also available pre-recorded) and Part Online **

This is the first segment (4 hr) of a three segment (16hr total), part in-person (optional) and part online, short course.

Segment 1 will be available both IN-PERSON on April 5 at the MSACL 2022 conference in Monterey, CA and ONLINE (pre-recorded) if you can't make it in person. Registration for Segment 1 is free (although to attend on-site you must be registered for MSACL 2022).

Segments 2 and 3 will take place ONLINE on April 29-30, 2022.

While the first SEGMENT is FREE, SEGEMENTS 2 and 3 that occur only ONLINE are fee-based. You can REGISTER HERE.

----------

Does Excel lag on you when you open a file bigger than 1000 rows? Has it ever changed your data to a date against your will? Are you ready to jump right past Tableau and into the world of Data Science using a real programming language?

Well, your wait is over because at MSACL we again 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.

The course will be run over three days (one in person to start and two online later) and time will be evenly split between didactic sessions and hands on problem solving with real data sets. Drs Holmes and Bunch 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

!!! DOWNLOAD PROGRAM PACKAGES PRIOR TO ARRIVAL ONSITE !!! THERE WILL NOT BE OPEN INTERNET WIFI IN THE CONFERENCE CENTER.

!!! POWER : Make sure your computer is charged to hold power for 4 hrs, as power outlets may not be available.

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. The major types of R variables: vectors (numerical, character, logical), matrices, data frames and lists.
  2. The important classes: numeric, character, list and changing between them
  3. Importing data from Excel
  4. Dealing with non-numeric instrument data
  5. Manipulating and cleansing your data
  6. Exporting data to Excel-like format.
  7. Basics of tidyverse: dplyr, filter, mutate, join
  8. Regressions: ordinary least squares,Passing Bablok, Deming, weighted regressions.
  9. Non-linear regressions
  10. Looping: Doing things repeatedly
  11. group_by and summarize
  12. Writing your own functions
  13. Making highly customized figures with base plot or ggplot
  14. Putting it all together projects:
  15. Preparing method comparison regression and Bland Altman plots
  16. Preparing mass spectrometry data for upload to LIS.
1854
Tuesday
800
950
Short Course: LC-MSMS 101 : Hands-On Training Session (GROUP 1)
@ Colton

Judy Stone, MT (ASCP), PhD, DABCC
UCSF

Jacqueline Hubbard, PhD, DABCC
QualiTox Laboratoires

Adina Badea, PhD, DABCC
Lifespan Health/Rhode Island Hospital & The Warren Alpert Medical School of Brown University

Robert Fitzgerald, PhD, DABCC
University of California San Diego

Sponsored in part by:


** Supplemental Hands-On Segment In-Person : Main Course is Online **

This is the supplemental bonus segment (2 hr) of a 16 hour online short course taking place on March 11-14, 2022. Attendance at this in-person segment is free, but REQUIRES pre-registration (separate from conference registration, coming soon) with priority given to online course registrants. There will be two instances of this segment (Group 1 and Group 2, both the same), with each to be capped at 20 participants.

You can register for the online course (fee-based) here.

----------

Is this workshop for you?

This two hour workshop is a supplement to the MSACL Online Short Course – “Getting Started with Quantitative LC-MS/MS in the Diagnostic Laboratory (LC-MS 101)”. The short course will be offered online, March 11-14, 2022 (register here). The hands-on workshop content is designed for attendees from the online short course, but the short course is not a prerequisite. Anyone starting out with quantitative LC-MS troubleshooting may find it useful.

Format and Content

The first 50 min session will include brief instructor demonstrations and then ample hands-on time for attendees to practice troubleshooting tasks, such as
- cutting (and recutting) PEEK tubing correctly
- connecting (and reconnecting) PEEK fittings to LC columns, other components
- changing LC pump check valves
- changing LC injection valve rotor seals
- reviewing chromatography problems caused by leaks, tubing/fitting mistakes and damage, excess LC dead volume, and aged LC components

The second 50 min session is a discussion of real world instrument troubleshooting cases from the instructors’ laboratories. Aside from the examples presented, the goal is to develop a standardized approach to troubleshooting complex LC-MS systems, including
- Know your LC flow path and LC components, how to avoid damaging the MS/MS
- How to look for leaks and sources of overpressure
- Using chromatogram overlays, pressure traces, maintenance chart review, system suitability testing and MS/MS infusion to locate the problem within the instrument

1850
Tuesday
900
1200
Workshop : How to Convince Admin THEY Want to Buy You a Mass Spectrometer
@ De Anza 2

Joshua Hayden, PhD, DABCC, FACB
Norton Healthcare

Juan David Garcia, MBA MT
University Of Texas Medical Branch


Objectives

The objective of this workshop is to give attendees the knowledge necessary to put together a convincing business case for purchasing a mass spectrometer. This knowledge will be imparted by presenting and discussing successful and unsuccessful examples of such business cases. Throughout the course, essential business terminology will be presented and explained.

Summary

Many laboratorians can discuss the benefits of implementing mass spectrometry into the clinical laboratory. From improved confidence in results to minimization of interferences, there are substantial and well-discussed benefits to mass spectrometry. Unfortunately, mass spectrometers cost money and the individuals empowered to write checks rarely relate to such technical justifications. This workshop is designed to help clinical laboratorians understand what factors matter to financial decision makers. The presenters include a clinical laboratorian with experience successfully acquiring mass spectrometers and an experienced administrator with significant laboratory and financial expertise. The presenters will walk attendees through the process of preparing a business case. Attendees will be presented with numerous examples of business cases that need improved and the attendees will be given the chance to discuss what is wrong and what needs to be done to fix them. Attendees will also be given a chance to submit their own personal business cases ahead of time if desired. These can be discussed in private after the workshop or (with attendee permission) can be discussed in part as part of the workshop. The goal is to prepare attendees to put together and present a business case that supports the acquisition of a mass spectrometer in terms that matter to financial decision makers.

Syllabus/Topics

How to assemble the worst business case ever (and guarantee failure)
Attendees will begin the session with an introduction to the worst possible business case one can present. The numerous flaws will be pointed out and addressed in an effort to highlight the many ways business cases can go wrong.

From LCMS and qTOF to ROI and DEPR (speaking the language of finance)
After attendees have a chance to see what not to do, it will be time to discuss what administrators/finance officers are looking for in a business plan. The goal is that attendees walk away with an understanding of the important terms and metrics their business cases will be evaluated by. In addition, an overview of hospital accounting and do's and don't's of capital equipment purchasing will be given.

Estimating costs
The cost of a mass spectrometer is far more than the instrument itself. This section will help attendees begin to consider everything they need to account for when proposing how much mass spectrometry will cost- labor, supplies, service contract, etc.

Estimating reimbursement
This section will cover how to estimate revenue- whether it is insourcing from a reference lab or setting up a new service line. The importance of payer mix and inpatient vs outpatient will be addressed

What's wrong with my business case?
Ending where the course started, the final section will cover examples of business cases. These cases will be used to illustrate cases that are very strong and those with weaknesses that can be improved. If submitted by attendees ahead of time, these example cases will be anonymized versions of those submissions.

1896
Tuesday
1000
1150
Short Course: LC-MSMS 101: Hands-On Training Session (GROUP 2)
@ Colton

Judy Stone, MT (ASCP), PhD, DABCC
UCSF

Jacqueline Hubbard, PhD, DABCC
QualiTox Laboratoires

Adina Badea, PhD, DABCC
Lifespan Health/Rhode Island Hospital & The Warren Alpert Medical School of Brown University

Robert Fitzgerald, PhD, DABCC
University of California San Diego

Sponsored in part by:


** Supplemental Hands-On Segment In-Person : Main Course is Online **

This is the supplemental bonus segment (2 hr) of a 16 hour online short course taking place on March 11-14, 2022. Attendance at this in-person segment is free, but REQUIRES pre-registration (separate from conference registration, coming soon) with priority given to online course registrants. There will be two instances of this segment (Group 1 and Group 2, both the same), with each to be capped at 20 participants.

You can register for the online course (fee-based) here.

----------

Is this workshop for you?

This two hour workshop is a supplement to the MSACL Online Short Course – “Getting Started with Quantitative LC-MS/MS in the Diagnostic Laboratory (LC-MS 101)”. The short course will be offered online, March 11-14, 2022 (register here). The hands-on workshop content is designed for attendees from the online short course, but the short course is not a prerequisite. Anyone starting out with quantitative LC-MS troubleshooting may find it useful.

Format and Content

The first 50 min session will include brief instructor demonstrations and then ample hands-on time for attendees to practice troubleshooting tasks, such as
- cutting (and recutting) PEEK tubing correctly
- connecting (and reconnecting) PEEK fittings to LC columns, other components
- changing LC pump check valves
- changing LC injection valve rotor seals
- reviewing chromatography problems caused by leaks, tubing/fitting mistakes and damage, excess LC dead volume, and aged LC components

The second 50 min session is a discussion of real world instrument troubleshooting cases from the instructors’ laboratories. Aside from the examples presented, the goal is to develop a standardized approach to troubleshooting complex LC-MS systems, including
- Know your LC flow path and LC components, how to avoid damaging the MS/MS
- How to look for leaks and sources of overpressure
- Using chromatogram overlays, pressure traces, maintenance chart review, system suitability testing and MS/MS infusion to locate the problem within the instrument

1932
Tuesday
1000
1145
Workshop: Design of Experiments for Development and Optimization of LC-MS Clinical Diagnostic Assay
@ Steinbeck 1

Margret Thorsteinsdottir, PhD
Faculty of Pharmaceutical Sciences, University of Iceland

Finnur Eiriksson, PhD
ArticMass


Objectives

The objective of the workshop is to provide an introduction into design of experiments (DoE) for clinical application with special focus on optimization of MS-based bioanalytical assays. The workshop is focused on practical implementation of DoE and will demonstrate how method development of UPLC-MS/MS clinical diagnostic methods can become much more efficient by utilizing DoE.

Summary

The chemometric approach, design of experiments (DoE) is an efficient tool for development and optimization of UPLC-MS/MS for quantification of biomarkers in complex biological matrices. The UPLC-MS/MS platform is composed of several processes which involves many experimental factors that need to be simultaneously optimized to obtain maximum sensitivity with adequate resolution at minimum retention time. DoE offers a practical approach for performing experiments in accordance to predefined plan, modelling by empirical functions, and graphical visualization. Basic concept of DoE will be presented with emphasis on practical implementation of DoE which include the three main stages, screening, optimization, and robustness testing. Example from optimization of a UPLC-MS/MS method for clinical diagnostic purposes and therapeutic drug monitoring will be used to show the cost-effective benefit of DoE, where it allows the effect of variables to be assessed with only a fraction of the experiments that would be required by changing one-separate-factor-at-time (COST) approach. A fractional factorial design was used for experimental screening to reveal the most influential experimental factors. When multi-levels qualitative factors were included in the screening experiments D-optimal design was applied. Significant factors were studied via central composite design and related to sensitivity, resolution and retention time utilizing partial least square (PLS)-regression. A specific and reliable UPLC-MS/MS assay for simultaneous quantification of urinary 2,8-dihydroxyadenine (DHA) and adenine was optimized efficiently with DoE. The assay has been implemented for clinical diagnosis and therapeutic drug monitoring of patients with adenine phosphoribosyltransferase (APRT) deficiency, which is an inborn error of purine metabolism.

Syllabus
-- Design of Experiments (DoE) - Get it right from the beginning
-- Basic concept and assessment of DoE
-- Optimization of LC-MS based clinical assay by DoE

1941
Tuesday
1200
1400
Short Course & Workshop Lunch Mixer
@ Steinbeck Foyer
1907
Tuesday
1215
1345
Workshop: Ion Mobility in the Clinical Lab?
@ Steinbeck 1

Christopher Chouinard, PhD
Florida Institute of Technology

Robin Kemperman, PhD
Children's Hospital of Philadelphia


Objective

Workshop attendees will learn about the basic operating principles of various ion mobility techniques, the potential benefits and challenges to its routine implementation in the clinical lab, and several potential applications.

Summary

Ion mobility-mass spectrometry (IM-MS) has become a cornerstone of biomedical analysis, with applications ranging from isomeric small molecule differentiation to the study of protein structure and folding dynamics. Despite its many advantages, IM-MS has yet to see routine implementation in the clinical lab due to challenges in quantitation, limited universal standards, data processing software, and reproducibility across different IMS techniques/vendor platforms. This workshop will introduce the common IMS techniques (e.g., drift tube, traveling wave, FAIMS/DMS, etc.) and their operating principles, expanding upon the benefits of incorporating IMS into conventional LC-MS/MS workflows and discussing the challenges that have limited such incorporation. Finally, an overview of current applications (including metabolomics, lipidomics, and proteomics examples) will be provided.

Objective 1: Understand the basic operating principles of IMS and the differences between the different techniques (e.g., drift tube, traveling wave, FAIMS/DMS, etc.)

Objective 2: Recognize the benefits and limitations to incorporating IMS into conventional LC-MS/MS workflows in the clinic

Objective 3: Become familiar with current (and potentially future) applications of IMS to the clinical lab

Syllabus
1. Basic Operating Conditions of IMS: Electric field application, experimental conditions (temperature, pressure, gas composition)
2. Different IMS techniques: Drift tube/traveling wave, field asymmetric/differential mobility, emerging techniques (i.e., TIMS, SLIM, cIMS, etc.)
3. Applications: Current examples from metabolomics, lipidomics, and proteomics

1884
Tuesday
1400
1425
Welcome Orientation
@ De Anza

Chris Herold, PhD, MBA
MSACL

Stephen Master, MD, PhD
Children's Hospital of Philadelphia

Tim Garrett, PhD
University of Florida College of Medicine

Kara Lynch, PhD
University of California San Francisco

Alan Rockwood, PhD, DABCC
University of Utah, School of Medicine

Cory Bystrom, PhD
MSACL 2022 Chair,
Ultragenyx


Opening Orientation with (1) a brief welcome from Chris Herold, (2) a brief presentation from Stephen Master (President of AACC), (2) an introduction to our new JMSACL co-Editors-in-Chief, Kara Lynch and Tim Garrett (and acknowledgement of founding co-Editors-in-Chief, Alan Rockwood and Michael Vogeser, who brought the journal to this point), and (3) an official welcome from the Chair of the MSACL 2022 Steering Committee, Cory Bystrom.
1908
Tuesday
1425
1445
State of the Science
@ De Anza

Cory Bystrom, PhD
MSACL 2022 Chair,
Ultragenyx

Michael Angelo, MD, PhD
Stanford University School of Medicine

Kara Lynch, PhD
University of California San Francisco

Stefani Thomas, PhD, DABCC, NRCC
University of Minnesota

1939
Tuesday
1445
1500
Break
@ De Anza Foyer
1967
Tuesday
1500
1545
Beyond the Human Genome: A Million Person Precision Population Health Project
@ De Anza

Leroy Hood, MD, PhD
Institute for Systems Biology


The vision of this project is that we will develop the infrastructure to employ a data-driven approach to optimizing the health trajectory of individuals for body and brain. We have two large populations (5,000 and 10,000) that have validated this approach for body and brain health, respectively. These studies have led to us pioneering the science of wellness and prevention. This project will require the acquisition of key partners for execution, which will be delineated. We are approaching the Federal Government for funding, as we did for the first Human Genome Project. This project will lead to striking new knowledge about medicine, it will catalyze the initiation of start-up companies and it will catalyze a paradigm shift in healthcare from a disease orientation to a wellness and prevention orientation. This will catalyze the largest paradigm shift in medicine, ever.

Moderated by:

Daniel Holmes, MD, FRCPC
St. Paul’s Hospital

1847
Tuesday
1545
1600
Break
@ De Anza Foyer
1968
Tuesday
1600
1645
The Clinical Laboratory Perspective on Wellness Testing: Let’s Take a Look Under the Hood
@ De Anza

Geoff Baird, MD, PhD
University of Washington


As medical science continues to make gains in the elucidation of disease pathophysiology and the discovery of cures , some have questioned the value of dedicating dwindling financial resources to maintaining wellness rather than to fighting disease per se. While both approaches are meritorious and complementary, neither approach is alone sufficient to ensure the health of a population. One major problem with the focus on wellness is the Bayesian dilemma that the positive predictive value of clinical laboratory testing in apparently healthy people is often low, as the specificities of few clinical tests are high enough to ensure that most positive results are true. The impact of this dilemma on laboratory-based wellness approaches will be discussed.

Moderated by:

Daniel Holmes, MD, FRCPC
St. Paul’s Hospital

1900
Tuesday
1645
1700
Break
@ De Anza Foyer
1969
Tuesday
1700
1800
The Michael S. Bereman Award for Innovative Clinical Proteomics : Seeing the Forest for the Trees: Taking a Step Back to Move Proteomics Forward in the Clinical Lab
@ De Anza

Mari DeMarco, PhD, DABCC, FACB, FCACB
University of British Columbia

Sponsored by:


Want to run a new test in your clinical lab that takes multiple days to prep, has a complicated (and costly) calibration scheme, and a detection approach so selective it could miss the analyte of interest? If that doesn’t sound appealing, you would be in the majority! While the analytical advantages of mass spectrometry resulted in it decisively displacing ligand binding methods as the gold standard approach for protein quantitation, making progress on the routine testing front has taken additional effort. Here we look at how re-evaluating the status quo in clinical proteomics has helped us take leaps forward and implement protein mass spectrometry to improve patient care. About the Award

Moderated by:

Christopher Shuford, Ph.D.
Labcorp

Andy Hoofnagle, MD, PhD
University of Washington

1901
Tuesday
1800
2100
Opening Exhibits Reception
@ Exhibit Hall - Serra
1848
Tuesday
1900
2000
Mentor Booth Tours
@ Exhibit Hall - Serra

Meet at Poster #50
1979
2000
2100
Troubleshooting Poster Session
@ Exhibit Hall - Serra
20:00 @ poster #28a
A Stumbling Block of Harmonizing LC-MS/MS Assays in Clinical Laboratories
Hsuan-Chieh (Joyce) Liao
University of Washington
20:15 @ poster #28b
Morphine and Oxycodone Co-Positivity in Pain Management Urine Drug Testing
Stephen Roper
Washington University School of Medicine
20:30 @ poster #27a
Nonspecific Adsorption and Loss of 11-Nor-9-carboxy-Δ9-tetrahydrocannabinol. Dude, where’s my THC?
Triniti Jensen
ARUP
20:45 @ poster #27b
Interfering Peak in the Estradiol (E2U) LC-MS/MS Assay
Mima Geere
UCSF
Tuesday
2100
2200
Hospitality Lounge
@ Jacks

Inside of Jacks Club Room (Portola Hotel)
1849

Wednesday

Wednesday
630
Registration Desk Opens
@ De Anza Foyer
1912
Wednesday
700
745
Round Table Interest Groups
@ De Anza Foyer

(1) On Being a Reviewer
with Tim Garrett

(2) Follow on discussion about convincing admin that they need to buy a mass spectrometer
with Joshua Hayden

(3) Shortcomings / Limitations of Antinuclear Antibodies (ANA) : Stark Disparities - Multiplex Vs. Immunofluorescence Assay
with Mahesheema Ali

(4) Tissue Imaging
with Michael Angelo, Laura Sanchez, David Herold

1913
Wednesday
800
855
Glycoproteins as Biomarkers for Cancers
@ De Anza

Carlito Lebrilla, PhD
UC Davis


The path from fundamental discoveries with MS to translation and commercialization.

Moderated by:

Laura Sanchez, PhD
University of California, Santa Cruz

1855
Wednesday
900
930
How Can Proteomics Fulfill the Unmet Needs of Effective Drug Treatment Stratification for Patients with Ovarian Cancer?
@ De Anza

Stefani Thomas, PhD, DABCC, NRCC
University of Minnesota


The mutational status of a solid tumor can predict the therapeutic efficacy of a specific drug in a molecularly defined subset of patients. Targeted therapies are available to treat advanced (stage II – IV) ovarian cancer with mutations in BRCA1/2 genes. Unfortunately, there is considerable inter-patient heterogeneity in BRCA1/2–based determinations of drug treatment sensitivity. Determining the proteome-level mechanisms of drug treatment sensitivity could enhance our ability to select the ovarian cancer patient populations that would benefit the most from these targeted therapies, consequently improving survival and overall treatment response. Our laboratory is applying mass spectrometry-based proteomics to identify protein signatures of drug treatment sensitivity and subsequent patient stratification for treatment. This presentation will provide an overview of the experimental models and analytical approaches that we are utilizing toward a long-term goal of identifying prognostic protein biomarkers of drug treatment sensitivity in patients with high-grade serous ovarian cancer.

Moderated by:

Laura Sanchez, PhD
University of California, Santa Cruz

1891
Wednesday
930
945
Coffee Break
@ Exhibit Hall - Serra
1966
Wednesday
945
1015
N-linked Glycans in Human Disease: From New Tools to Translational and Preclinical Studies
@ De Anza

Peggi Angel, PhD
MUSC Proteomics Center


N-glycosylation plays a significant role in immune cell recruitment, influences disease progression and outcome and response to therapy. Here, we discuss simplified workflows capable of reporting N-glycan expression patterns in tissues, cells and biofluids. We present translational and pre-clinical work investigating glycosylation patterns in cardiovascular disease, cancer risk and cancer. A long-term goal is to leverage glycosylation patterns to non-invasively monitor disease status and therapeutic efficacy.

Moderated by:

Laura Sanchez, PhD
University of California, Santa Cruz

1950
Wednesday
1015
1100
Panel Discussion
@ De Anza

Moderated by:

Laura Sanchez, PhD
University of California, Santa Cruz

1892
Wednesday
1100
1200
Poster Session
@ Exhibit Hall - Serra
1856
1200
1300

Industry Workshop(s)

Thermo Fisher Scientific
@ De Anza 1 (Track 1)

Mass Spectrometry-based Tools Empowering the State of Healthcare – Today and Tomorrow

Part 1 : From the OR to the Microbiology Lab: Advanced Development of the MasSpec Pen for Broad Clinical Use
Mary King, PhD Candidate – Prof. Livia S. Eberlin Group
The University of Texas at Austin
Part 2 : Enhanced LC-MS Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Peptides
Richard Gibson, PhD
Thermo Fisher Scientific

Thermo Fisher Scientific
@ De Anza 2 (Track 2)

A Wide Range of Mass Spec Solutions for the Clinical Laboratory : From Flexibility for LDTs to a New Fully Automated Clinical Analyser for Easy Implementation

Part 1 : LC-MS/MS Adoption in the Clinical Laboratory : Current Trends and Future Perspectives
Kara Lynch, PhD
University of California San Francisco
Part 2 : Measuring Vitamin D2 and D3 on the Cascadion™ Fully Automated LC-MS/MS System : From Installation to Result Reporting
Philip Sobolesky, PhD
Santa Clara Valley Medical Center

Agilent Technologies
@ De Anza 3 (Track 3)

Keeping an “Eye on” Mobility Technologies for Clinical Research Laboratory Workflows
Frederick Strathmann, PhD, MBA
MOBILion Systems
Automated Rapid Throughput Quantitative Proteomics of Amniotic Fluid Utilizing Agilent AssayMap Bravo and UHPLC-MS/MS
Anita Vinjamuri, Bachelors of Science in Chemistry
University of California Davis
Armin Oloumi, BS in Biochemistry
University of California, Davis

Wednesday
1300
1400
Poster Session
@ Exhibit Hall - Serra
1860

Scientific Session 1

Track 1
De Anza 1

Endogenous Small Molecules

Chair
Brian Keevil
University Hospital of South Manchester
2nd
Jayson Pagaduan
Intermountain Healthcare

Track 2
De Anza 2

Glycomics and Proteomics of SARS-CoV2 Immunology

Chair
Rebecca Bearden
Cleveland Clinic

Track 3
De Anza 3

Taking it to the Top: Reference Methods and Materials

Chair
Karen Phinney
NIST
2nd
Andrew T Nelson
University of Texas Southwestern

Track 4
Bonzai

Practical Training

Session CLOSED

1400
1420
Ultrafast Integrated UPLC-MS/MS Second-tier Newborn Screening for Inborn Errors of Propionate, Cobalamin, and Methionine Metabolism
Joshua Dubland
The University of British Columbia & BC Children’s Hospital
Rational Design of Serological Diagnostics Using Immunoprecipitation-Targeted Proteomic Assays
Andrei Drabovich
University of Alberta
Internal Standard Approaches: Stable Isotope-labeled Intact, Winged or Peptide
Kayla Moehnke
Mayo Clinic
CLOSED
1420
1440
Newborn Screening for Vitamin B12 Deficiency: Is it Justified? Is it Possible?
Bojana Rakic
BC Children’s Hospital, Vancouver, Canada
Afucosylated IgG Responses to BNT162b2 mRNA Vaccine Against Sars-CoV-2 Differ in Naïve and Antigen-experienced Individuals
Tamas Pongracz
Leiden University Medical Center
Development of a Candidate Reference Measurement Procedure for Urine Albumin Using LC-MS/MS
Jesse Seegmiller
University of Minnesota
CLOSED
1440
1500
Urine Free Cortisol by LC-MS/MS: Monitoring Known Interferences as Potential Culprits of Iatrogenic Cushing’s Syndrome
Julie Ray
ARUP Labs
A Targeted Multiplex MRM LC-MS/MS Immunoassay for Characterisation of Antibody Response to SARS CoV2 Vaccination
Ivan Doykov
University College London
Get Your Reference Right!: Synthesis, Certification, and Confirmation of the First Reference Material for (-)-trans-11-nor-9-Carboxy-Δ9-THC beta-d-glucuronide
Raymond Suhandynata
University of California, San Diego
CLOSED
Wednesday
1500
1515
Coffee Break
@ Exhibit Hall - Serra
1971

Scientific Session 2

Track 1
De Anza 1

Rapid Detection and Quantitation via Ambient Ionization

Chair
Vishnu Samara
UCLA

Track 2
De Anza 2

Tissue imaging - Dynamics and Mapping

Chair
Peggi Angel
MUSC Proteomics Center
2nd
James Weatherill
The University of Edinburgh

Track 3
De Anza 3

Starting Right - The Life of a Sample from Tube to Bench

Chair
Michael Chen
University of British Columbia

Track 4
Bonzai

Practical Training

1515
1535
Rapid Detection of Anticoagulants Using Coated Blade Spray Mass Spectrometry
Briana Fitch
University of California San Francisco
Mass Spectrometry Imaging of Glutathione Biosynthesis Heterogeneity Using Multiple Infusion Start Times and IR-MALDESI
Allyson Mellinger
North Carolina State University
Tracking the Stability of Clinical Blood Plasma Proteins with ΔS-Cys-Albumin—a Dilute-and-shoot LC-MS-based Marker of Specimen Exposure to Thawed Conditions
Chad Borges
Arizona State University
Oral Fluid as Alternative Matrix for Drug Testing: Clinical Utility and Method Development
Adina Badea
Lifespan Health/Rhode Island Hospital & The Warren Alpert Medical School of Brown University
1535
1555
Concomitant Quantification of Methotrexate and its Metabolites in Serum Samples via Fully Automated Coated Blade Spray-Tandem Mass Spectrometry Workflow
German Gomez
Restek
Mass Spectrometry Histochemistry of Human FFPE Material Getting Ready for the Clinic
Peter Verhaert
ProteoFormiX
The Decisive Role of Pre-analytical Sample Handling When Investigating the Lipidome in Clinical Research
Daniel Kratz
Institute of Clinical Pharmacology, Pharmazentrum Frankfurt/Zafes, University Hospital of Goethe-University
...
Extended Session
...
1555
1615
Rapid Urine Drug Testing by Direct Analysis in Real-Time (DART)-Mass Spectrometry
Ibrahim Choucair
Yale School of Medicine
Improving Accuracy and Speed of MALDI MSI for Clinical Translation
Sankha (Bobby) Basu
Brigham and Women’s Hospital
The Essence of a Streamlined Process for Large-Scale Quantitative Protein Mass Spectrometry
Renee Ruhaak
LUMC
...
Extended Session
...
Wednesday
1615
1630
Coffee Break
@ Exhibit Hall - Serra
1972

Scientific Session 3

Track 1
De Anza 1

Steroids - Methods and Matricies

Chair
Claire Knezevic
Johns Hopkins University

Track 2
De Anza 2

Proteomics - New Methods and Continuous Improvement

Chair
Mari DeMarco
University of British Columbia

Track 3
De Anza 3

Data - Integrating, Mapping and Reporting

Chair
Patrick Vanderboom
Mayo Clinic

Track 4
Bonzai

Practical Training

1630
1650
Application of a Novel Steroidomic LC-MS/MS Method for Investigating Metabolic Alterations in Patients with Non-Alcoholic Fatty Liver Disease
Federico Ponzetto
University of Turin
Proteomic Analyses of Malaria Drug Resistance
Annie Moradian
Precision Biomarker Laboratories
Data Integration Pipeline for Multi-Batch Untargeted Lipidomics Studies
Khyati Mehta
Cincinnati Children’s Hospital/University of Cincinnati
Transition Ratio Monitoring for the Masses
Russell Grant
Labcorp
1650
1710
Ion Mobility-Mass Spectrometry: Targeted Steroid Applications in the Clinical Lab
Christopher Chouinard
Florida Institute of Technology
Integrating Lipidomics and Proteomics for Increased Diagnostic Accuracy in Prostate Cancer
Lee Gethings
Waters
The Chemistry of Our Blood: Mapping Circulating Molecules to the Landscape of Human Health and Disease
Nicholas Bevins
Sapient Bioanalytics
...
Extended Session
...
1710
1730
Salivary Cortisone in the Assessment of the HPA Axis
Brian Keevil
University Hospital of South Manchester
High Sensitivity Measurement of Thyroglobulin Using Conventional Flowrate LC-MS/MS
Mark Kushnir
ARUP Institute for Clinical & Experimental Pathology
Using Data Independent Acquisition to Inform the Development of Cerebrospinal Fluid Triple Quadrupole Assays
Deanna Plubell
University of Washington
...
Extended Session
...
Wednesday
1730
1830
Happy Hour in the Exhibit Hall
@ Exhibit Hall - Serra
1864
1745
1815
Troubleshooting Posters
@ Exhibit Hall - Serra
17:45 @ poster #29a
Interfering Compound in Urine Cannabinoid Analysis
Agnes Cua
Precision Diagnostics
18:00 @ poster #29b
Communicating Proteogenomics Data to Physicians
John Koomen
Moffitt Cancer Center
Wednesday
1830
Dinner on Own
@ Off-site

Check out one of the many restaurants on Alvarado Street.
1865
Wednesday
1830
1930
Hospitality Reception
@ Jacks

Inside of Jacks Club Room (Portola Hotel)

Meet up with friends for light drinks on your way out to dinner at one of the many restaurants on Alvarado Street.

1977
Wednesday
1845
2200
FeMS Networking Event - Separate Registration Required
@ Ferrantes

Visit Reg Desk to inquire if interested in participating.
1919

Thursday

Thursday
630
Registration Desk Opens
@ De Anza Foyer
1909
Thursday
700
745
Round Table Interest Groups
@ De Anza Foyer

(1) JMSACL co-Editors-in-Chief (Tim Garrett & Kara Lynch): Current and Interested Editors and Reviewers Round-Up

(2) Meet a Clinical Chemist with Shannon Haymond and Stephen Master

(3) Tissue Imaging Satellite Conference Discussion with Michael Angelo & David Herold

1914
Thursday
800
855
Proteins in Space: Statistical Approaches to Understand the Spatial Organization and Structure of Proteins in Complex Tissues
@ De Anza

Barbara Engelhardt, PhD
Princeton University


Spatial single-cell technologies have enabled the comprehensive study of complex tissues and organs at a single-cell level. However, the statistical methods to perform analyses have not kept pace with the technologies for measuring spatially-resolved genes and proteins in tissue samples. In this talk, I will present two methods that allow the study of spatially-resolved proteomics data. First, nonnegative spatial factorization develops a low-dimensional representation of the spatially-resolved samples to identify variation in protein expression across space. Second, Gaussian process spatial alignment allows multiple slices from different technologies to be aligned to a known or unknown common coordinate system, enabling the construction of a tissue atlas from disparate samples of that tissue type.

Moderated by:

Shannon Haymond, PhD
Northwestern University Feinberg School of Medicine

1911
Thursday
855
900
Analytik Jena Industry Brief (5m)
@ De Anza

MALDI-TOF-MS sample preparation – A comprehensive view of automated liquid handling concepts
James Bond
1953
Thursday
900
915
Coffee Break
@ Exhibit Hall - Serra
1964
Thursday
915
1000
Statistical Considerations for Biomarker Discovery Experiments: From a Model Organism to Clinical Study
@ De Anza

Meena Choi, PhD
Genentech


Quantitative mass spectrometry-based proteomics is a technology of growing importance in biological and clinical research. As modern quantitative mass spectrometry-based proteomics workflows become complex and diverse, it requires statistical considerations, methods, and computational tools for experimental planning and data analysis to reduce bias and inefficiencies and maximize the reproducibility of results. This talk will highlight statistics essential for proteomics experiments and considerations for designing a proteomics experiment for biological research biomarker discovery and issues related to large quantitative proteomic datasets generated by diverse types of acquisition of proteomics. Also, this talk will present the comprehensive mass-spectrometry proteomics-based strategy and case studies for the clinical protein biomarker development, from a model organism to large-scale clinical samples, with rigorous experimental design and statistical analysis.

Moderated by:

Shannon Haymond, PhD
Northwestern University Feinberg School of Medicine

1875
Thursday
1000
1015
Coffee Break
@ Exhibit Hall - Serra
1965
Thursday
1015
1100
Adapting to the New Normal: Navigating the Rollercoaster of SARS-CoV-2 Testing Needs While Building Long Term Capabilities
@ De Anza

Patrick Mathias, MD, PhD
University of Washington


The COVID-19 pandemic has been a challenging time for clinical laboratories, but it has also improved awareness of the important role labs play across health care and public health domains. The University of Washington Department of Laboratory Medicine and Pathology has worked to establish diagnostic SARS-CoV-2 testing as a widely available resource over a large footprint of our state by combining expertise in laboratory testing and informatics with community partnerships to expand testing access and convenience. Over the course of the pandemic the needs of our laboratories as well as of the public and of public health authorities have evolved. Staffing and supply chain challenges have placed a greater emphasis on efficiency and productivity. The need for genomic surveillance of the evolving virus has required a close integration of clinical workflows with research-focused genomics workflows. Increased demand for services coupled with record high positivity rates during the omicron surge has challenged our model for expanding capacity using sample pooling. This presentation will describe the evolution of our testing program and infrastructure amidst these challenges, highlighting the informatics capabilities we needed to adapt. Finally, we will discuss what needs and capabilities are likely to persist beyond the pandemic and how the lessons we have learned can better equip laboratories to improve the health of the public.

Moderated by:

Shannon Haymond, PhD
Northwestern University Feinberg School of Medicine

1961
Thursday
1100
1200
Poster Session
@ Exhibit Hall - Serra
1869
1200
1300

Industry Workshop(s)

Thermo Fisher Scientific
@ De Anza 1 (Track 1)

Advances in High Throughput Mass Spectrometry – Novel Front-End Solutions Driving Routine Clinical TDM Analysis

Part 1 : A Therapeutic Drug Monitoring Assay of Immunosuppressants using TurboFlow LC and High-Resolution Mass Spectrometry
Y. Ruben Luo, PhD, DABCC
Stanford University
Part 2 : High Throughput Paper-Spray Mass Spectrometry (PS-MS) for Validated Clozapine Therapeutic Drug Monitoring in Human Serum
Chris Gill, Ph.D.
Vancouver Island University

Indigo BioAutomation
@ De Anza 2 (Track 2)

Data Analytics, Change Management and Elevating Laboratory Performance
Romeo Solano, Ph.D.
Quest Diagnostics
Laboratory Analysis as a Team Sport
Jim Edwards
Indigo BioAutomation
Indigo BioAutomation Females in Mass Spectrometry Annual Award Winners
Randall Julian, PhD
Indigo BioAutomation

Shimadzu
@ De Anza 3 (Track 3)

Do More with Less: Ease the Burden of Staff Shortages while Simultaneously Boosting Lab Productivity with Ultra-Fast Mass Spectrometry
Scott Kuzdzal, Ph.D., Analytical Chemistry
Shimadzu Scientific Instruments
Scaling Up while Scaling Down: New Era for Plasma/Serum Proteomics
Benoit Fatou, PhD
Boston Children's Hospital, Harvard Medical School

Thursday
1300
1400
Poster Session
@ Exhibit Hall - Serra
1870
Thursday
1400
Exhibits Closed
@ Exhibit Hall - Serra
1874

Scientific Session 4

Track 1
De Anza 1

Microbiology - Identification and Metabolomics

Chair
Jeff Whitman
UCSF

Track 2
De Anza 2

Monitoring mAb

Chair
Y. Ruben Luo
Stanford University
2nd
Rashmi Kumar
Stanford University

Track 3
De Anza 3

Making the Most of the Data We Harvest

Chair
Paula Ladwig
Mayo Clinic
2nd
Jennifer Kemp
Mayo Clinic

Track 4
Bonzai

Practical Training

1400
1420
Identification of the Subspecies from Mycobacterium Abscessus Complex by MALDI-TOF MS and Machine Learning Approach
David Rodriguez-Temporal
Hospital General Universitario Gregorio Marañón, Madrid, Spain
View Slides (PDF)

Therapeutic Antibody Monitoring: the Case of Infliximab
Maria Willrich
Mayo Clinic
Development and Implementation of a Web-based Application for Urine Drug Testing and Improving Resulting Workflow
Abed Pablo
University of Washington
Working Smarter Not Harder on Sample Prep
Matthew Crawford
Labcorp
1420
1440
Unique Chemical Biology Tools for Metabolomics Analysis – Exploring Gut Microbiota Metabolism
Daniel Globisch
Uppsala University
Development and Validation of a Bioanalytical Method for Certolizumab Pegol (Cimzia) Drug Using Surface Plasmon Resonance
Brett Holmquist
Labcorp
Machine Learning-based Fragment Selection Improves Performance of Qualitative PRM Assays for Viral Pathogen Screening
Patrick Vanderboom
Mayo Clinic
...
Extended Session
...
1440
1500
Investigating Microbial Cooperation and Metabolic Communication During Clostrioles Difficile Infection Using Imaging Mass Spectrometry
Boone Prentice
University of Florida
Measurement of Therapeutic and Anti-drug Antibodies Using Biolayer Interferometry
Kara Lynch
University of California San Francisco
Isotopic Distribution Calibration for Mass Spectrometry
Anthony Maus
Mayo Clinic
...
Extended Session
...
Thursday
1500
1515
Break
@ De Anza Foyer
1973

Scientific Session 5

Track 1
De Anza 1

Vitamin D

Chair
Julie Ray
ARUP Labs
2nd
Amol Bajaj
ARUP

Track 2
De Anza 2

Drugs of Abuse

Chair
Melissa Budelier
TriCore Reference Laboratories
2nd
Imir Metushi
UCLA

Track 3
De Anza 3

Late-Breaking Submissions A

Chair
Kamisha Johnson-Davis
University of Utah and ARUP

Track 4
Bonzai

Practical Training

1515
1535
Learning from Vitamin D Binding Protein
Andy Hoofnagle
University of Washington
Analysis of Suspected Opioid Overdose Samples Using High Resolution Mass Spectrometry (HRMS) for Public Health Opioids Biosurveillance Program in South Carolina
James LaPalme
SC PHL
Detection of Mycobacterial from Species to Sub-strain Level with Pathogen-derived Peptidomes
Tony Hu
Tulane University School of Medicine
Introduction to Clinical Proteomics Using Mass Spectrometry
Timothy Collier
Quest Diagnostics
1535
1555
Free 25-hydroxy Vitamin D Measured by LC-MS/MS in Healthy Adults and Individuals with Kidney Disease
Mark Kushnir
ARUP Institute for Clinical & Experimental Pathology
Opioid Overdose Harm Reduction Drug Checking and Illicit Drug Supply Surveillance by On-site Paper Spray Mass Spectrometry (PS-MS)
Chris Gill
Vancouver Island University
Novel First Trimester Biomarkers of Fetal Growth Restriction Identified by Next Generation Proteomics of Maternal Plasma
Nandor Gabor Than
Research Centre for Natural Sciences, Budapest, Hungary
...
Extended Session
...
1555
1615
Clinical Utility of Measuring the Vitamin D Metabolome including 24,25-(OH)2D3 by LC-MS/MS
Martin Kaufmann
Queen’s University
Opiate Drug Testing Does Not have to be a “pain in the MLS”: How a Second-generation LC-MS/MS Assay Improved Workflow for Drug Testing and Sign-out
Hsuan-Chieh (Joyce) Liao
University of Washington
Precise Quantitation of PTEN by Immuno-MRM: A Tool to Resolve the Breast Cancer Biomarker Controversy
Christoph Borchers
Jewish General Hospital, McGill University Montreal, QC, Canada
...
Extended Session
...
Thursday
1615
1630
Break
@ De Anza Foyer
1974

Scientific Session 6

Track 1
De Anza 1

Multiplexing Small Molecules and Glycans

Chair
Allyson Mellinger
North Carolina State University

Track 2
De Anza 2

Top-Down Protein Characterization

Chair
Timothy Collier
Quest Diagnostics

Track 3
De Anza 3

Late-Breaking Submissions B

Chair
Gwen McMillin
University of Utah and ARUP
2nd
Danting Liu
St. Jude Children’s Research Hospital

Track 4
Bonzai

Practical Training

1630
1650
Targeting Cellular Nucleotide Biosynthesis Using Ultrahigh-Performance Liquid Chromatography Coupled with High Resolution Mass Spectrometry
Xueheng Zhao
Cincinnati Children’s Hospital Medical Center
Discovery of a Biomarker for beta-Thalassemia by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and Proton Transfer Reaction- Parallel Ion Parking
Yuan Lin
Florida State University
Mitochondrial and Metabolic Dysfunctions in Neurons Carrying the 22q11.2 Deletion
Wojciech Michno
Stanford University / University College London
Free Climb or Free Solo: Guidance and Accounts of Establishing Reference Intervals for LDT Mass Spectrometry Assays
Elizabeth Frank, Kelly Doyle
University of Utah Health / ARUP Laboratories
1650
1710
Tumor Associated Carbohydrate Antigens (TACAs) as Promising Targets for the Development of Immunotherapy for Colorectal Cancer
Katarina Madunić
Leiden University Medical Centre
Capillary Zone Electrophoresis Coupling with High-resolution Mass Spectrometry for Top-down Structural Characterization of Hemoglobin Variants
Y. Ruben Luo
Stanford University
Correlation of Genotyping and Phenotyping with the IGF-1 assays for Growth Hormone disorders
Ravinder Singh
Mayo Clinic
...
Extended Session
...
1710
1730
Serum Bile Acid Profiling by UHPLC-MS/MS Predicts Cholesteric Pruritus Reduction in Maralixibat Treated Patients with Bile Salt Export Pump Deficiency
Kenneth Setchell
Cincinnati Children’s Hospital Medical Center
Detection of an Unusual IGF-2 Species Using High-resolution Mass Spectrometry During a Routine IGF-1 Clinical Assay
Ievgen Motorykin
Quest Diagnostics
Mapping the 3 D Proteome Using Surface Accessibility in Animal Models of Disease
John Yates
Scripps Research Institute
...
Extended Session
...
Thursday
1745
2000
Dinner & British-Style Trivia Night with Tim
@ San Carlos
1943
Thursday
2000
After Hours Activity Suggestions
@ Off-site

*These are non-MSACL-sponsored activities.

Alvarado Beer Garden.

Club Cibo - $5 drinks all night.

1917

Friday

Friday
700
800
Monterey Challenge Run/Walk
@ De Anza Foyer

Meet-up in front of Registration in De Anza Foyer. Advice: Once on path, go left towards Cannery Row.
1878
Friday
800
Registration Desk Opens
@ De Anza Foyer
1910
Friday
900
1000
Addressing Hurdles in Clinical Translation of Targeted Proteomics
@ De Anza

Jeffrey Whiteaker, PhD
Fred Hutchinson Cancer Research Center


Quantifying proteins and post-translational modifications will improve precision medicine, but several hurdles remain to adopting proteomics to the clinical laboratory. Dr. Whiteaker will discuss successes and remaining challenges for incorporating targeted proteomic measurements in clinical trials and other clinical applications.

Moderated by:

Stefani Thomas, PhD, DABCC, NRCC
University of Minnesota

Timothy Collier, PhD
Quest Diagnostics

1879
Friday
1000
1030
Newborn Screening by Mass Spec Meets Newborn Screening by DNA Sequencing
@ De Anza

Michael Gelb, PhD
University of Washington


Our laboratory has been developing tandem mass spectrometry (MS/MS) for worldwide expansion of newborn screening (NBS) panels to include an ever-increasing collection of treatable genetic diseases. There is widespread discussion on the use of whole genome and whole exome DNA sequencing in population-wide NBS. The intersection of biochemical- and DNA-based NBS is an interesting topic now under heavy discussion.

We will highlight the development of liquid chromatography-MS/MS (LC-MS/MS) for multiplex NBS of a large panel of treatable genetic diseases in newborns. Next generation sequencing (NGS) is also employed currently as a second-tier analysis after LC-MS/MS assays. We will also illustrate how it is possible to carry out first-tier NGS followed by second-tier LC-MS/MS NBS.

LC-MS/MS is used together with enzyme substrates and biomarkers to monitor the activity of a large collection of enzymes and to measure the abundance of biomarkers in dried blood spots on NBS cards. We will focus on multiplex methods and then zoom in one a more detailed analysis of one disease called metachromatic leukodystrophy (MLD). We carried out a pilot MLD NBS study and determined that the rate of false positives out of 28,000 newborns screened is essentially zero showing the power of LC-MS/MS for NBS of this lysosomal storage disorder. In the second arm of the study, we have been measuring the activity of the enzyme relevant to MLD on a large collection of gene variants that are found in allele databases and for which no pathogenic information is reported. We show how we can integrate these efforts to provide for a highly efficient NBS program for MLD.

We screened ~28,000 newborns for elevated sulfatide lipid, the biomarker that is relevant to MLD and found 180 high sulfatide newborns. These were submitted to an assay of the activity of the relevant enzyme, arylsulfatase A, and all but two showed normal levels of activity. DNA sequencing was carried out on 2 newborns, one with 0% and one with 8% of normal ARSA activity. The newborn with 0% activity was confirmed to have MLD, the other was shown to not have MLD. On the DNA front, we created a phenotype matrix that allows one to input the ARSA enzymatic activity of each variant to provide a composite genotype, and to make a prediction of the phenotype associated with this genotype. We show that this method is 83% accurate at predicting the true set of phenotypes observed in MLD patients.

Massively multiplexed NBS of genetic diseases in newborns is possible using LC-MS/MS, and when used with second-tier NGS leads to a successful NBS platform. We show that it is also possible to carry out NGS as a first-tier NBS step and to clarify the results with second-tier biochemical assays based on LC-MS/MS. Thus LC-MS/MS meets DNA and DNA meets LC-MS/MS, and this provides a framework for the future employment of both LC-MS/MS and NGS in expansion of population based NBS.

Moderated by:

Stefani Thomas, PhD, DABCC, NRCC
University of Minnesota

Timothy Collier, PhD
Quest Diagnostics

1880
Friday
1030
1050
Coffee Break
@ De Anza Foyer
1963
Friday
1050
1120
Utilization of Mass Spectrometry to Discover and Develop Novel Biomarkers to Support Drug Development
@ De Anza

Veronica Anania, PhD
Genentech


Biomarkers play an important role in the drug development process including providing necessary insights into target engagement, dose selection and mechanism of action of candidate therapeutics. LC-MS is uniquely positioned to enable accurate quantitation of both small and large molecule biomarker candidates, however, the process of going from biomarker discovery to a multiplexed targeted MRM panel in clinical samples is long and resource intensive. Moreover, biomarker candidates often fail to replicate when tested in large clinical cohorts. Recent advances in data-independent MS (DIA-MS) have made this technology more accessible and certain benefits of DIA-MS including reproducible label-free analysis of hundreds of samples, ability to capture low abundance ions over a high dynamic range, and deep proteome coverage makes this technology well suited to streamline translational proteomics. One major hurdle for using DIA-MS to support drug development is that the quantitative range for most DIA-MS methods has not been well characterized and thus, quantitative conclusions drawn by prior studies that have employed this approach have been controversial. Here, we describe challenges associated with applying DIA-MS methods to address questions associated with clinical development and introduce best practices for establishing quantitative criteria for DIA-MS approaches in clinical trial samples. Results and lessons learned from both discovery and targeted clinical biomarker studies will be discussed and a model for a more streamlined biomarker development workflow that conserves resources and provides more comprehensive proteomic information from clinical trial samples will be discussed.

Moderated by:

Stefani Thomas, PhD, DABCC, NRCC
University of Minnesota

Timothy Collier, PhD
Quest Diagnostics

1948
Friday
1120
1155
Panel Discussion
@ De Anza

Moderated by:

Stefani Thomas, PhD, DABCC, NRCC
University of Minnesota

Timothy Collier, PhD
Quest Diagnostics

1881
Friday
1155
1200
Closing Statements
@ De Anza
1949
Friday
1200
1400
Boxed Lunch Pick-Up and Mixer
@ Jacks

Pickup a boxed lunch and enjoy a little down time or check out the workshop starting in Bonsai at 1215.
1882
Friday
1215
1345
Workshop: Rethinking the Traditional Workflow for Urine Toxicology Testing
@ Bonsai

Melissa Budelier, PhD
TriCore Reference Laboratories

Benjamin Beppler
TriCore Reference Laboratories


Objectives

- Identify common challenges with reflexive urine drug screening
- Discuss the utility of 'hybrid' testing and direct to definitive testing using mass spectrometry
- Address the importance of drug panel test selection, and the potential issues with specific drug classes
- Describe the value of providing interpretive reports for urine drug testing, particularly for pain management clients

Workshop Summary

Many clinical laboratories continue to utilize a traditional urine drug testing algorithm involving an initial screen, typically via an automated immunoassay, followed by confirmation of positive and/or unexpected results using mass spectrometry. This algorithm emerged in the 1970s and 1980s from the desire to test for the use of illicit substances in the military and other workplaces. It was designed to answer the question: Are employees upholding a drug-free workplace? This algorithm presents significant limitations in many clinical situations, particularly in the areas of pain management and substance use disorder treatments, where the primary question changes to: Is my patient taking their medication as prescribed? This workshop will discuss several alternatives for urine drug testing, such as direct to mass spectrometry testing and 'hybrid' panels. It will also discuss considerations for selecting the appropriate analytes for urine drug testing panels and potential pitfalls associated with certain classes of drugs. Finally, it will introduce our recent efforts to implement the use of interpretive reporting for pain management clients.

1940
Friday
1400
1700
Workshop: Pre-analytical considerations as prerequisite for successful clinical application of lipidomics
@ De Anza 1

Robert Gurke, PhD
Fraunhofer Institute for Translational Medicine and Pharmacology ITMP

Bo Burla, PhD
Sling @ National University of Singapore

Margret Thorsteinsdottir, PhD
Faculty of Pharmaceutical Sciences, University of Iceland

Anne K. Bendt, PhD
Singapore Lipidomics Incubator (SLING), National University of Singapore


Objectives

It is the objective of the workshop to provide an introduction into pre-analytical considerations for clinical application of MS-based analytics, with a special focus on lipids. However, these considerations are in many cases independent of specific analytes of interest and can hence be applied for polar metabolites as well as proteins. The workshop is focused on main hurdles to be considered when performing clinical research using LC-MS based determination of lipids namely: (I) pre-analytical sample handling, (II) frequent generation of patient samples as well as (III) overall cohort and study design.

Summary

Lipids are involved in a broad spectrum of functionalities in the organism and implicated in a variety of physiological and pathological processes. Changes in lipid levels are promising biomarkers for early diagnosis, prognosis of disease progression, or guidance for selecting promising therapeutic approaches. However, biomarker discovery in the field of lipidomics is a very challenging process since lipids require specific procedures regarding sampling (including selection of sample type and collection procedures, storage conditions and number of freeze-thaw cycles), sample preparation and analysis for reliable determination. As especially pre-analytical sample handling is a critical step for the reliable analysis of the lipidome, a close cooperation with the clinicians is necessary. This ensures following a highly standardized protocol for venous blood sampling to avoid several pre-analytical pitfalls potentially changing the lipid profile ex vivo. As collecting venous blood samples is very laborious for patients as well as clinicians, other ways for a more frequent sample collection are necessary. Therefore, capillary blood sampling using microsampling devices is an auspicious way to complement the strategy of analyzing venous blood-based samples taken in the clinics. Besides considering the right sampling strategy, the structured recording of sampling details and subject metadata, the overall planning of the study and also the cohorts to be included is of high relevance. All mentioned points have to be considered before starting a clinical research project applying lipidomics to generate high quality data making biomarker discovery possible.

Syllabus
- Pre-Analytical factors influencing lipid concentrations
- Capillary vs. venous blood sampling - the potential of microsampling
- Cohort & Study design for lipidomics in clinical research

1883
Friday
1400
1800
Short Course: LC-MSMS 201 : Understanding and Optimization of LC-MS/MS to Develop Successful Methods for Identification and Quantitation in Complex Matrices
@ De Anza 2

Robert Voyksner, PhD
LCMS Limited


** Part In-Person and Part Online **

This is the first segment (4 hr) of a 16 hour, part in-person and part online, short course.

Segments 2, 3 and 4 will take place ONLINE on April 22-24, 2022.

While attending this IN-PERSON segment is FREE, the ONLINE attendance is fee-based. You can REGISTER HERE.

----------

This course is designed for the chromatographer / mass spectrometrist who want to be successful in developing methods, method optimization and solving problems using LC/MS/MS. The course covers the atmospheric pressure ionization (API) techniques of electrospray, pneumatically assisted electrospray and atmospheric pressure chemical ionization (APCI) and atmospheric pressure photo ionization (APPI) using single quadrupole, triple quadrupole, time-of-flight and ion trap mass analyzers.

Discussions of sample preparation and chromatography will target method development and optimization for the analysis of "real-world" samples by LC/MS/MS.

The course highlights the following topics with respect to optimization a method to achieve the best sensitivity, specificity and sample throughput:

  1. Optimization ionization in API techniques,
  2. understanding and minimizing matrix suppression,
  3. relative merits of various LC column lengths, particle sizes and column diameters for LC/MS/MS analysis,
  4. introduction into the interpretation of MS/MS spectra,
  5. important issues in LC/MS/MS quantitation, and
  6. optimization of an quantitative analysis.

Applications of LC/MS/MS to analyze compounds of clinical interest in biological matrices will be discussed throughout the course to emphasize the topics covered.

1904
Friday
1400
1800
Workshop: CLSI C64 - Supporting development of quantitative protein and peptide assays for clinical use
@ De Anza 3

Cory Bystrom, PhD
MSACL 2022 Chair,
Ultragenyx

Russell Grant, PhD
Labcorp


* with Special Guest Stars *

Objective:
Workshop attendees will gain an understanding of the clinical assay development framework for proteins and peptides established in CLSI C64. Using C64 as a framework for development will help the laboratorian approach protein and peptide assay development confident that analytical performance will meet clinical requirements.

Summary:
The development and validation of quantitative assays for proteins and peptides for clinical use is a significant undertaking and presents challenges that are distinct from small molecules. The heterogeneous nature of proteins and the frequent requirement to use proteolysis aided workflows add complexity that require careful attention to definition The workshop will be an interactive discussion covering each chapter in C64, guided by authors that contributed extensively to the development of the document.

Objective 1: Understand the holistic process of delivering a clinically relevant LC-MS/MS protein/peptide assay from inception to validation.

Objective 2: Recognize the factors in assay development that are unique to proteins and peptides in comparison to traditional small molecule assays.

Objective 3: Understand key experimental requirements for successful development and validation.

Syllabus:
1. Introduction to C64, philosophy and scope
2. Interactive discussion of each chapter

1885
Friday
1400
1800
Short Course: Sample Prep 201 : Sample Preparation and Alternative Matrices for LC-MS Assays
@ Bonsai

William Clarke, MBA, PhD
Johns Hopkins University School of Medicine

Mark Marzinke, PhD
The Johns Hopkins Hospital


** Part In-Person and Part Online **

This in-person activity is Segment 2 (4 hr) of a 3 segment (12 hour total), part in-person and part online, short course.

Segments 1 and 3 will take place ONLINE on March 4 & April 22, 2022. The first segment is before the conference, the third segment is after the conference.

While attending this IN-PERSON segment is FREE, the ONLINE attendance is fee-based. You can REGISTER HERE.

----------

This course highlights not only the importance of sample processing in the clinical laboratory environment, but also illustrates the "fit for purpose" application of processing techniques in clinical mass spectrometry. This course discusses the theory behind different specimen preparation methods, strengths and weaknesses of each approach, as well as opportunities for automation.

The first 4 hour online segment will cover workshop ground rules, introduction, pain points of LC-MS, specimen processing (tube types, management, etc.), and matrix effects.

The second 4 hour in-person segment will cover dilution and protein precipitation, solid phase extraction, supported liquid extraction, liquid-liquid extraction, and affinity-based sample preparation

The third 4 hour online segment (online) will elaborate on the foundations established in the first two segments, and expand into newer technologies and automated alternatives for sample processing.

Specific topics to be covered include:

  1. Pain points in clinical LC-MS
  2. Overview of specimen processing in laboratory medicine
  3. Off-line sample processing
  4. On-line sample processing
  5. Analysis of blood and urine
  6. LC-MS of tissue specimens
  7. Alternate body fluid specimens (e.g. CSF, breast milk, etc.)
  8. Dried specimens as matrices
  9. Automation of sample processing

Topics will be covered through lecture, Q&A, Case Studies, and small group exercises.

1898
Friday
1400
1800
Short Course: Data Science 201 : Going Further With R: Tackling Clinical Laboratory Data Manipulation and Modeling
@ Colton

Patrick Mathias, MD, PhD
University of Washington

Shannon Haymond, PhD
Northwestern University Feinberg School of Medicine


** Part In-Person and Part Online **

This is the first segment (4 hr) of a 16 hour, part in-person and part online, short course.

Segments 2, 3 and 4 will take place ONLINE on April 28,29 and 30, 2022

While attending this IN-PERSON segment is FREE, the ONLINE attendance is fee-based. You can REGISTER HERE.

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Having completed your first steps into the wonderful world of data analysis with R (Data Science 101 with Daniel Holmes), 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 course will be run over two days and time will be split between lecture sessions, individual problem solving, and a highly interactive group-level data mining of real data sets (there may even be prizes). 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 to bring a laptop with the R language installed and R Studio interface installed. Students may use Windows, Mac OSX or Linux environments. Both R and R studio are free (as in “Free Beer”) and open-source.

Students should be prepared continue to expand their skill in programming – which, as you learned in the introductory course 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

!!! DOWNLOAD PROGRAM PACKAGES PRIOR TO ARRIVAL ONSITE !!! THERE WILL NOT BE OPEN INTERNET WIFI IN THE CONFERENCE CENTER.

!!! POWER : Make sure your computer is charged to hold power for 4 hrs, as power outlets may not be available.

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 data analysis
  2. Introduction to version control
  3. Using R Markdown for reproducible reports
  4. Advanced file reading capabilities
  5. Scaling up your data transformation skills
  6. Cleaning dirty data and managing timestamps
  7. Joining data sets together
  8. Connecting R to databases
  9. Prediction with linear regression and classification with logistic regression
1903
Friday
1800
2000
Closing Dinner Reception
@ Jacks

Jacks Club Room
1887
Friday
2000
After Hours Activity Suggestions
@ Off-site

*These are non-MSACL-sponsored activities.

Alvarado Brewery.

Club Cibo - $5 drinks all night.

1893