Publications by authors named "M MacCoss"

Targeted mass spectrometry (MS) methods are powerful tools for the selective and sensitive analysis of peptides identified in global discovery experiments. Selected reaction monitoring (SRM) is the most widely accepted clinical MS method due to its reliability and performance. However, SRM and parallel reaction monitoring (PRM) are limited in throughput and are typically used for assays with around 100 targets or fewer.

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Article Synopsis
  • Data-independent acquisition (DIA) mass spectrometry is gaining popularity in quantitative proteomics due to its effectiveness in data analysis.
  • Creating reliable spectral libraries for DIA is challenging, as most current libraries come from data-dependent acquisition (DDA) data or predictions based on DDA.
  • The study introduces Carafe, a tool that generates specific spectral libraries by using deep learning directly on DIA data, showing better performance in predicting ion intensity and detecting peptides compared to existing DDA models.
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Article Synopsis
  • This study identifies the formation of covalent protein adducts from drug metabolism as significant risk factors for adverse drug reactions and cytochrome P450 enzyme inactivation.
  • It introduces a novel liquid chromatography with tandem mass spectrometry (LC-MS/MS) approach to detect low abundance drug-protein adducts in human liver microsomes, using raloxifene as a model.
  • The findings reveal adducts in multiple proteins, including CYP enzymes, and suggest that some adducts may be harmless, providing a framework for better understanding the human adductome related to drug exposure.
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Brain microvascular dysfunction is an important feature of Alzheimer's disease (AD). To better understand the brain microvascular molecular signatures of AD, we processed and analyzed isolated human brain microvessels by data-independent acquisition liquid chromatography with tandem mass spectrometry (DIA LC-MS/MS) to generate a quantitative dataset at the peptide and protein level. Brain microvessels were isolated from parietal cortex grey matter using protocols that preserve viability for downstream functional studies.

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Sex has a major effect on the metabolome. However, we do not yet understand the degree to which these quantitative sex differences in metabolism are associated with anatomical dimorphism and modulated by sex-specific tissues. In the fruit fly, , knocking out the () gene gives rise to adults with intermediate sex characteristics.

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