Proteomics Strategies to Develop Proteins of Post-translational Modifications in Plasma-Derived Extracellular Vesicles as Disease Markers

Blood tests, which are the most wide spread diagnosis procedure in clinical analysis, apply blood biomarkers to categorize patients and support treatment decisions. However, existing biomarkers often lack specificity and are far from comprehensive. Mass spectrometry-based proteomics allow users to characterize plasma protein in great depth and has become a powerful tool in the biomarker discovery area. However, because of the extremely high dynamic range of plasma, being able identify thousands of plasma proteins using methods such as Liquid chromatography-tandem mass spectrometry (LC-MS/MS) remains a challenge. Furthermore, recent discoveries of extracellular vesicles (EVs) have proven that EVs have a high possibility for becoming the source for biomarker discovery and disease diagnosis. In addition to the protein in EVs, post-translation modification proteins (PTMs proteins) are also interesting targets because the PTMs proteins are involved with many cancer-related signaling transductions. This dissertation proposes proteomics strategies of using PTMs proteins in plasma-derived extracellular vesicles as breast cancer markers. Initially, Chapter One highlights the potential of using phosphoproteins in extracellular vesicles as markers for breast cancer. Chapter Two delves into the development of a pipeline proteomics strategy that utilizes glycoproteins in EVs as breast cancer markers. Finally, Chapter Three explores the details of different subtypes, which presents the possibility of leveraging three PTMs including phosphorylation, acetylation and glycosylation to distinguish three major breast cancer subtypes

Search for intermediate-mass black hole binaries in the third observing run of Advanced LIGO and Advanced Virgo

International audienceIntermediate-mass black holes (IMBHs) span the approximate mass range 100−105 M⊙, between black holes (BHs) that formed by stellar collapse and the supermassive BHs at the centers of galaxies. Mergers of IMBH binaries are the most energetic gravitational-wave sources accessible by the terrestrial detector network. Searches of the first two observing runs of Advanced LIGO and Advanced Virgo did not yield any significant IMBH binary signals. In the third observing run (O3), the increased network sensitivity enabled the detection of GW190521, a signal consistent with a binary merger of mass ∼150 M⊙ providing direct evidence of IMBH formation. Here, we report on a dedicated search of O3 data for further IMBH binary mergers, combining both modeled (matched filter) and model-independent search methods. We find some marginal candidates, but none are sufficiently significant to indicate detection of further IMBH mergers. We quantify the sensitivity of the individual search methods and of the combined search using a suite of IMBH binary signals obtained via numerical relativity, including the effects of spins misaligned with the binary orbital axis, and present the resulting upper limits on astrophysical merger rates. Our most stringent limit is for equal mass and aligned spin BH binary of total mass 200 M⊙ and effective aligned spin 0.8 at 0.056 Gpc−3 yr−1 (90% confidence), a factor of 3.5 more constraining than previous LIGO-Virgo limits. We also update the estimated rate of mergers similar to GW190521 to 0.08 Gpc−3 yr−1.Key words: gravitational waves / stars: black holes / black hole physicsCorresponding author: W. Del Pozzo, e-mail: [email protected]† Deceased, August 2020