Chinese American Society for Mass Spectrometry - Bruker Webinar

Join the upcoming webinar organized by the Chinese American Society for Mass Spectrometry and Bruker!

Explore the latest breakthroughs in proteomics and metabolomics, from top-down strategies for proteoform analysis to illuminating the dark metabolome, plus exciting advances in 4D-Proteomics™ with Bruker Daltonics. Don’t miss this opportunity to gain fresh insights into the future of molecular science.

8:00 - 8:25 am Decoding a Book with 86% of the Words Missing: Toward Solutions for the Dark Metabolome
Pieter Dorrestein, Ph.D., Professor, UC San Diego, San Diego, CA, USA

Abstract:
Despite advances in high-resolution mass spectrometry and computational tools, only ~14% of molecular features detected in human samples can be confidently annotated, leaving the vast majority of the “dark metabolome” uncharacterized. This gap is akin to attempting to interpret a book where more than four out of five words are missing - enough to sense fragments of meaning, but insufficient to follow the full story. Existing pathway maps, largely derived from mid-20th century biochemistry, capture only a narrow portion of human chemical space and fail to account for the complexity introduced by diet, microbiomes, environment, and xenobiotics. Here we discuss the current state of metabolomics, the challenges of annotation and integration, and the urgent need for scalable strategies - including synthetic libraries, Data science-driven structural inference, and global data harmonization - to begin filling in the missing words. Only by reconstructing the unseen majority can we transform metabolomics from a fragmented narrative into a coherent story of human biology and health.

8:25 - 8:50 am Top-down Proteomics: Ready for Prime Time?
Ying Ge, Ph.D., Professor, University of Wisconsin-Madison, Madison, WI, USA

Abstract:
Proteoforms — the diverse protein products resulting from genetic variations, alternative splicing, and post-translational modifications — play pivotal roles in biology and disease. Top-down proteomics (TDP) analyzes intact proteoforms, enabling deeper insights into molecular mechanisms and advancing precision medicine. However, challenges such as protein solubility, proteome complexity, and analytical sensitivity have hindered broader adoption of TDP. In this seminar, I will present our multi-faceted approach to address these challenges through innovative strategies. We have developed new MS-compatible surfactants for improved protein solubilization, novel materials and methodologies for enhanced multi-dimensional chromatography separation, and nanomaterials for enriching low-abundance proteins. Additionally, I will highlight our recent advancements in high-sensitivity LC-MS methods, including a high-sensitivity TDP platform for single-cell proteoform analysis that reveals cellular heterogeneity. Our development of small-scale serial size exclusion chromatography (s3SEC) coupled with capillary RPLC-MS/MS has enabled comprehensive proteoform coverage from minimal sample inputs. Currently, we are developing a multi-dimensional liquid chromatography approach that incorporates multiple orthogonal separation modes to expand proteome coverage and detect proteins and protein complexes directly from human heart tissues for native TDP. Furthermore, I will describe our newly developed native nanoproteomics strategy for enriching and characterizing endogenous protein complexes directly from human heart tissue. Lastly, I will introduce our new comprehensive user-friendly software package for both denatured and native TDP data analysis. These advancements collectively address the challenges of TDP, paving the way for broader adaptation of TDP to achieve deeper insights into complex biological systems and improved understanding of disease mechanisms.

8:50 - 9:00 am Advances in 4D Proteomics with Bruker Daltonics
Shourjo Ghose, Ph.D., Director of Proteomics North America, Bruker Scientific LLC, MA, USA

Abstract:
Data independent acquisition became the most widely used method for proteomics due to its high level of sensitivity, reproducibility, and data completeness. To increase sensitivity and sample throughput, a lower number of broader isolation windows needs be applied, which leads to reduced selectivity. The combination with ion mobility separations like Trapped Ion Mobility (TIMS) prior to quadrupole isolation increases selectivity, however the quadrupole has to switch its isolation position in multiple steps to follow the mobility separation. The talk focuses on the different melodies of the PASEF workflows that drives biology from plasma proteomics to single cell proteomics.