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• W4311192813 endingPage "44" @default.
• W4311192813 startingPage "27" @default.
• W4311192813 abstract "This review describes the development of the Molecular Microscope Diagnostic System (MMDx) for heart transplant endomyocardial biopsies (EMBs). MMDx-Heart uses microarrays to measure biopsy-based gene expression and ensembles of machine learning algorithms to interpret the results and compare each new biopsy to a large reference set of earlier biopsies. MMDx assesses T cell-mediated rejection (TCMR), antibody-mediated rejection (AMR), recent parenchymal injury, and atrophy-fibrosis, continually learning from new biopsies. Rejection-associated transcripts mapped in kidney transplants and experimental systems were used to identify TCMR, AMR, and recent injury-induced inflammation. Rejection and injury emerged as gradients of intensity, rather than binary classes. AMR was one-third donor-specific antibody (DSA)-negative, and many EMBs first considered to have no rejection displayed minor AMR-like changes, with increased probability of DSA positivity and subtle inflammation. Rejection-associated transcript-based algorithms now classify EMBs as Normal, Minor AMR changes, AMR, possible AMR, TCMR, possible TCMR, and recent injury. Additionally, MMDx uses injury-associated transcript sets to assess the degree of parenchymal injury and atrophy-fibrosis in every biopsy and study the effect of rejection on the parenchyma. TCMR directly injures the parenchyma whereas AMR usually induces microcirculation stress but relatively little initial parenchymal damage, although slowly inducing parenchymal atrophy-fibrosis. Function (left ventricular ejection fraction) and short-term risk of failure are strongly determined by parenchymal injury. These discoveries can guide molecular diagnostic applications, either as a central MMDx system or adapted to other platforms. MMDx can also help calibrate noninvasive blood-based biomarkers to avoid unnecessary biopsies and monitor response to therapy." @default.
• W4311192813 created "2022-12-24" @default.
• W4311192813 creator A5024196748 @default.
• W4311192813 creator A5072478271 @default.
• W4311192813 date "2022-12-08" @default.
• W4311192813 modified "2023-10-03" @default.
• W4311192813 title "The Molecular Microscope Diagnostic System: Assessment of Rejection and Injury in Heart Transplant Biopsies" @default.
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• W4311192813 doi "https://doi.org/10.1097/tp.0000000000004323" @default.
• W4311192813 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36508644" @default.
• W4311192813 hasPublicationYear "2022" @default.
• W4311192813 type Work @default.
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