A general theme in translational proteomics that involves first genotyping patients will be presented. Some peptide-driven assays for histone modifications in cancer epigenetics will be presented, along with whole-protein (i.e., top down proteomic) measurements of high value targets like KRAS. Assays deployed in clinical research are typically developed and validated with basic studies ofisogenic cell-based models of colorectal cancer, multiple myeloma, and glioblastoma. Current state-of-the-art in whole protein mass spectrometry will be presented, along with the state of play in assessing the value of proteoform-resolved measurements in clinical research and biomarker discovery & verification.

Various configurations of MALDI mass spectrometry have been developed for rapid detection of unprocessed microorganisms on the battle field. Recently this direct approach has been approved by the FDA for use in clinical microbiology. Automated data processing has a critical role in both of these applications, and both library matching and proteomic bioinformatics have been developed to identify bacteria based on their mass spectra. This presentation will include a historical overview of the biomarkers, including phospholipids and proteins, which can be observed directly from unprocessed bacteria and yeast using many different ionization methods. Observations will be offered on strategies for sample enrichment. Current limitations and challenges for mass spectrometry-based strategies will be discussed.

A comprehensive understanding of molecular patterns of health and disease is needed to pave the way for personalized medicine and tissue regeneration. The best way to capture disease complexity is to chart and connect multilevel molecular information within a tissue using mass spectrometry and data algorithms. this molecular tissue-typing using imaging mass spectrometry provides unique insights in patterns of health and disease. Mass spectrometry based molecular information is impacting clinical research and diagnosis in various disciplines, ranging from pathology to surgical care. Molecular detail provided by translational imaging mass spectrometry is demonstrated to directly benefit patient cure and care.

High parameter single cell analysis has driven deep understanding of immune processes. Using a next-generation single-cell “mass cytometry” platform we quantify surface and cytokine or drug responsive indices of kinase target with 45 or more parameter analysis (e.g. 45 antibodies, viability, nucleic acid content, and relative cell size). Similarly, we have developed two advanced technologies that enable deep phenotyping of solid tissue in both fresh frozen and FFPE formats (50 – 100 markers). We have recently extended this parameterization to mRNA with the capability to measure down to 5 molecules per cell in combination with any other set of previously created markers.

I will present evidence of deep internal order in immune functionality demonstrating that differentiation and immune activities have evolved with a definable “shape”. This shape is altered during immune surveillance and “imprinted” during, and after, pathogen attack, traumatic injury, or auto-immune disease. Hierarchies of functionally defined trans-cellular modules are observed that can be used for mechanistic and clinical insights. I will focus upon pathogen attack, traumatic surgical intervention in human, and auto-immune processes for the presentation.