01 Top Down Proteomics and Top Down Mass Spectrometry: Emerging Technologies
Top-Down Proteomics Interest Group
Presiding: Joe Cannon; Caroline DeHart; Frederik Lermyte
Top down (TD) protein mass spectrometry (MS), when performed optimally, provides unique information that is not accessible with more sensitive bottom up methods. While conceptually simple, there are technical challenges that must be overcome to perform a successful TD experiment or analysis. In this workshop, we will invite experts in industry and academia to showcase new technological advances from separations to MS to bioinformatics that broaden the utility of TD-MS and TD proteomics. There will be emphasis on educating the greater community on new capabilities in the field that increase sensitivity, throughput, and the amount of information achievable. We will focus on new separation technologies that are used for intact protein analysis, on MS advances that facilitate more quantitative or informative analyses, on new computational approaches, and finally on the application of some of those new technologies. Each topic will be introduced by a short presentation, followed by audience discussion and debate. Please contact workshop chairs if you are interested in presenting an introduction to spark the discussion of a topic.
02 HDX, Covalent Labeling & Cross-Linking: New developments and Applications
HDX Covalent Labeling & Cross Linking Interest Group
Presiding: Miklos Guttman; Fabio Gozzo; Corie Ralston
Developments in MS instrumentation, sample preparation strategies, reagents and informatics tools have significantly advanced applications of HDX, covalent labeling and cross-linking approaches in protein structural and interaction analysis. This workshop will feature invited speakers with expertise in HDX, chemical labeling, and cross-linking methods to introduce each methodology, discuss ongoing developments, highlight any strengths and limitations, and point out things to see while at ASMS related to these methods. The second part of the workshop will focus on exciting new technical developments within HDX/XL/CL-MS through 5 min talks from invited members of the community. The speakers will form a panel for the last portion of the workshop to address questions including an opportunity for novices/students to contribute anonymous questions on fundamentals. One of the organizers will oversee the online portion of the workshop to support the 'hybrid' format of the meeting this year.
03 Recent Advances in Oligonucleotides & Peptides Bioanalysis by Triple Quad and HRMS
Regulated Bioanalysis Interest Group
Presiding: Jian Wang; Dian Su
Room 201 ABC
There were nine oligonucleotide and fourteen peptide drugs approved by Food and Drug Administration (FDA) from 2016 to 2020. Particularly with the recent approval of two oligonucleotide and four peptide (one antibody-drug conjugate) therapeutics in 2020, we are looking forward to seeing expanded interests in medium-size therapeutics. The 2021 ASMS Regulated Bioanalysis Interest Group (RBIG) Workshop is focused on "Recent Advances in Oligonucleotides & Peptides Bioanalysis by Triple Quad and HRMS". We would like to build our discussion on the conclusions and recommendations from the 2018 White Paper in Bioanalysis: https://www.future-science.com/doi/pdf/10.4155/bio-2018-0268
"...LC-MS/MS and HRMS analysis, selection of an IS that matches chemistry and stereochemistry (if necessary)with the aim to obtain the same extraction efficiency as the analyte, is challenging; To increase sensitivity, double liquid-liquid extractions using phenol and chloroform combination or SPE, IA enrichment, or selecting multiple target ions are options but should be carefully evaluated;..."
"The use of quantitative HRMS over unit resolution MS is analyte and matrix dependent. One option to improve sensitivity for therapeutic peptides analysis can be to sum multiple MRM as long as specificity/selectivity has been carefully evaluated; the signal to noise ratio needs to increase when summing multiple transitions;..."
This workshop will develop future discussions and consensus on Regulated Bioanalysis of oligonucleotides & peptides including topics on sample preparation, Mass Spectrometric methods and data processing. Experts in the field will share their experience in this highly interactive workshop.
04 Bridging Native-MS in Academia and Industry: Nucleic Acids and Their Delivery Systems
Native Mass Spectrometry Interest Group
Presiding: Michael Marty; Iain Campuzano; Elizabeth Hecht
Room 204 ABC
Since the initial experiments performed in academia demonstrating the retention of noncovalent protein-ligand and protein-protein complexes in the gas-phase, native MS has grown into a fully established research field. This unique area has given rise to the development of specialized MS hardware for the transmission and detection of ultra-large ions and methods allowing characterization of complex and emerging pharma modalities and new research targets.
Interest in the therapeutic use of nucleic acids in a variety of forms has grown significantly since its first clinical trials in the early 1990s. The recent unprecedented advances in mRNA vaccines represents the success of one class of nt. based drugs that also includes siRNA, nucleic acid conjugates, and aptamers.
Although native MS has most commonly been employed to study protein complexes, a small community has driven significant advances in native MS of nucleic acids. Beyond the nucleic acids themselves, the delivery vehicle can be critical to the success of nucleic acid therapeutics. A wide range of potential delivery options are available, ranging from antibody conjugates, lipid nanoparticles, polymer networks/gels, or viral capsids. Native mass spectrometry is uniquely suited to characterize these complex systems and support research and development for novel nucleic acid therapeutics.
Within this workshop, we will discuss the diversity of nucleic acid-based systems now being studied by native-MS in both academia and pharma and the new technologies for studying these complex systems. Our focus is to bridge new technology and applications development in both academic and pharma research environments, allowing for routine project support and progression for modalities that require native MS analytics.
05 The NIH and NSF Review and Funding Process
Presiding: Salvatore Sechi; Kelsey Cook; Douglas Sheeley; Kenneth Ryan
Room 102 AB
Many ASMS members and conference participants are supported by the National Institutes of Health or the National Science Foundation. During this workshop the general funding and review process of grant applications/proposals will be presented. Issues like identifying the best contacts, writing an effective application/proposal, and responding to the reviewers' criticisms will be discussed. Speakers will explore these issues from the perspectives of the applicant, reviewer, and administrator, with some emphasis on new investigators and training opportunities. Tips on grant writing and insights into the review process will be presented. The session will also provide an opportunity to inquire about the latest initiatives and priorities. Substantial time will be allotted for discussion and questions.. NIH and NSF staff will also be available for individual discussions with investigators during scheduled "Office Hours" in the poster exhibit hall.
06 Big Data: Analytics and Metadata for Energy, Petroleum and Biofuels
Energy Petroleum & Biofuels Interest Group
Presiding: Amy McKenna; Leonard Nyadong
Room 103 ABC
The burgeoning trend in big data analytics (BDA), which allows speedy and efficient examination of large amounts of data to uncover hidden patterns, correlations and other insights presents a new frontier for energy research. In the case of fossil, biofuels, and other complex organic mixtures (e.g., natural organic matter, emerging contaminants) high resolution mass spectrometry-based approaches play a vital role for detailed molecular-level characterization. However, the ability to uncover information from high resolution mass spectra data sets is being pushed to the limits of instrumentation and methodological capabilities. These analyses often routinely generate over 50,000 peaks in the case of crude oil, which challenges data analyses. Most of the data analytics tools developed for data visualizing, which include Kendrick mass defect and van Krevelen analyses and other statistics analyses are limited to only a few data sets. Big data analytics in the petroleum and biofuels field provides opportunity to uncover novel correlations in the molecular-level analytical measurements to macroscopic behavior to enable enhanced upgrading value. Big data analytics include collecting data from different sources, which can be very challenging in terms of compatibility, using the right data and the right tools to make the right decisions in real time. Several types of tools are often required to work together to collect, process, cleanse, and analyze big data.
This workshop will focus on an open discussion format with panelists to jumpstart conversations on the challenges and enablers for application of big data analytics in the petroleum and biofuels field. The discussions will focus on some of the prerequisites for developing big data analytics capability, which include: (1) Finding the right tools and platforms; (2) Making big data accessible; (3) Maintaining quality data; and (4) Keeping data secure; and (5) Types of metadata required for each sample type. The workshop will consist of short three-four slides by each panelist, followed by an open forum question and answer and discussion.
07 Quality Control for Proteomics and Metabolomics
Presiding: David Tabb; Wout Bittremieux
Room 104 AB
Throughout biological mass spectrometry, researchers are prioritizing repeatability and reproducibility of experimentation. This workshop, presented by members of the HUPO PSI (Proteomics Standards Initiative) Quality Control Working Group, will demonstrate methods in quality control (QC) and quality assurance for mass spectrometry.
The presentations and discussions will emphasize real-life scenarios, using published experiments as a starting point. The team will demonstrate how to transform a collection of LC-MS/MS raw data into quality metrics and how to make inferences or decisions based upon these metrics (such as recognizing batch effects and outliers). The mzQC file format created by this team to communicate quality information will be shown in action, enabling software tools from different laboratories to communicate.
Some of the questions we hope to answer with participants include the following: How can QC samples be incorporated in your experimental design? How do different sample processing steps influence the measured data, for example, by inadvertently introducing artificial modifications? Is it possible to disentangle the influence of technical and biological variability? Which user-friendly software tools are available to assess data quality?
08 New Horizons in the Application of Mass Spectrometry in Extractables and Leachables
Presiding: Atish Sen; Douglas Kiehl; Stephen Warren
Room 108 AB
Mass spectrometry is now integral to the analysis of extractables and leachables in the pharmaceutical, food and environmental industries. Extractables and leachables analysis has now become an essential part of specifications on release, stability and life cycle management for both small molecule and biologics drug products. Regulatory organizations are giving increased scrutiny to E&L with rapidly evolving expectations. Mass spectrometry being an important tool in identifying and assessing E&L compounds originating from packaging, manufacturing and drug delivery systems. This workshop will discuss advances in the use of MS and related techniques for achieving comprehensive characterization and profiling of E&L.
09 Allyship: Embracing Diversity and Inclusion in Your Workplace
Career Development Interest Group
Presiding: Lucinda Hittle; Troy Wood
Room 109 AB
As we look to truly embrace diversity and inclusion in the workplace, developing and strengthening our ability to serve as an ally for others is essential. This interactive workshop will focus on specific workplace scenarios through small group breakout discussions. Participants will have a chance to learn steps to active allyship, do's and don'ts, and collectively discuss their challenges and lessons learned. This workshop is designed to bring together mass spectrometrists from all environments including, but not limited to, mass spectrometry vendors, chemical, pharmaceutical, forensic and academic scientists. Attendees will be divided into small groups for break-out discussions. Participants will have the opportunity to rotate through these small group sessions in a "speed dating" format to discuss as many scenarios as possible and enhance networking. Each small group will have an experienced scientist and facilitator. All are welcome.
10 Data Independent Acquisition: From Data Acquisition to Analysis
Data Independent Acquisition Interest Group
Presiding: Florian Meier; Lindsay Pino
Room 110 AB
In recent years, data independent acquisition (DIA) schemes have become increasingly popular as they promise high levels of reproducibility and data completeness in large sample cohorts, suitable for systems biology and translational research.
With advances in the latest generation of mass spectrometers and liquid chromatography systems, the scale of DIA experiments has dramatically increased through the combination of shorter chromatography gradients with the speed of time-of-flight. This is also facilitated by emerging acquisition schemes such as scanning quadrupole-type or ion mobility-enhanced methods. These trends have also fueled the development of faster, more scalable, and user-friendly software, including support for advanced data structures. Larger datasets also come with statistical challenges that have not been fully investigated for label-free quantitative mass spectrometry data, such as normalization, batch effect correction, and significance testing for complex experimental designs.
At the same time, the range of applications for DIA is continuously expanding, for example, to the quantitative analysis of post-translational modifications beyond phosphorylation, including ubiquitination and acylation. PTM analysis may further benefit from new fragmentation methods. Although some work has been done to expand DIA to other areas of mass spectrometry such as small molecule and imaging proteomics, these approaches have not been fully implemented and are areas of active research.
In this workshop, we invite experts in the field to discuss technological and software innovations, as well as promising biological and medical applications. The open format should engage discussions about unique challenges, but also opportunities for future developments.
11 Emerging Technologies Advancing Mass Spectrometry Research: 3D Printing
Presiding: Kristof B. Cank, Herma C. Pierre
Room 111 AB
This workshop series will concern the use of auxiliary technologies that support advancements in the field of MS. 3D printers allow for quick prototyping this quickly finding their way into laboratories. Discussion at the workshop will focus on the implementation of 3D printing to support MS research.
12 Big Particles - Practical Aspects to Trapping Ultra High Masses
Ion Trap MS Interest Group
Presiding: Theresa Evans-Nguyen; Dalton Snyder
Room 113 ABC
Extending the mass range of ion traps to large particles such as virions and protein complexes seems particularly relevant in the age of COVID. At first glance, the shift in application of ion traps to high mass analysis requires a simple shift to lower frequency fundamental waveforms. However, nuances of space-charge repulsion, collision cross-section, electronic instrumentation control, and detection methods are worth consideration. We will invite a panel of prominent researchers in the field to layout the current state of the art in ultra-high mass analysis by ion traps. Presentations will be solicited to identify the practical aspects and major challenges of using traps to explore the high mass regime. Following these presentations, we will open discussion to such topics as orthogonal technologies in spectroscopy, intersectional interest with aerosols, and bio-particle application needs. By focusing the use of ion traps explicitly on large particle analysis, we hope to foster wider interest, crowd-source new ideas, and encourage greater community and collaboration.
13 Probability-based Metabolite Identification Confidence: How Can We Get There?
Presiding: Thomas Metz; Oliver Fiehn; Gary Patti
In metabolomics studies, the determination of confidence in metabolite identifications is ultimately made by individual researchers. After applying tolerance thresholds for e.g. mass accuracy or MS/MS library scores, researchers manually perform comparisons and annotations, accepting or rejecting the results based on arbitrary or subjective criteria. The Chemical Analysis Working Group of the Metabolomics Standards Initiative (MSI) published in 2007 the first proposed minimum reporting standards for metabolite identification confidence, which consisted of four MSI-levels of confidence in decreasing order based on the amount and degree of orthogonality of the analytical information supporting the identification. While MSI-levels for assigning metabolite identification confidence can be refined and more detailed, neither confidence thresholds nor combining different levels of experimental and biological probabilities have been thoroughly tested. Unlike proteomics, robust workflows that result in solid FDR-associated automatic structure assignments are missing in metabolomics. New methods are needed that instead focus on probability-based assessments of identification along with methods for estimating identification false discovery and that remove the subjectivity on the part of the data reporter. In this workshop, we will discuss conceptual models for assigning a probability to quantify the evidence for the presence of a compound in a sample and that are ideally generalizable and transferable across measurement platforms and sources of evidence. The role of reference libraries and their impacts in terms of size and composition will also be discussed.
14 Achieving Harmonized Clinical Laboratory Testing: Current Best Practices & Future Approaches
Clinical Chemistry Interest Group
Presiding: Candice Ulmer; Donald Chace
Room 105 AB
To ensure high quality clinical laboratory testing, consistent disease diagnosis, and improved patient outcomes, the harmonization of processes for both screening and diagnostics must be achieved on a local, national, and international level. Discussions are needed on clinical laboratory best practice policies, procedures, and processes/systems to eliminate existing barriers and facilitate the comparability of laboratory information across the entire testing process. This workshop will  identify common QA/QC issues in clinical laboratory testing,  highlight current best practices for pre-analytical, analytical, and post-analytical process, and  discuss considerations for new approaches to harmonize clinical laboratory testing. In addition, this workshop will provide an overview of successful quality assurance programs in clinical testing from national and international stakeholder organizations.