The Utility of Spatial Transcriptomics for Solid Organ Transplantation

Li, Jennifer S Y; Raghubar, Arti M.; Matigian, Nicholas; Ng, Monica; Rogers, Natasha M.; Mallett, Andrew

doi:10.1097/tp.0000000000004466

Cited by 6 publications

(2 citation statements)

References 89 publications

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“…Multiple platforms have been reported in various organs generating excellent insights, for instance, in coronavirus disease-related collapsing glomerulopathy [51]. Briefly these are based either on in-situ sequencing (ISS) or in-situ hybridization (ISH) [52]. While ISH based methods like MERFISH can be performed on paraffin-embedded archived biopsies, ISS methods require dedicated fresh frozen sections.…”

Section: Spatial Transcriptomicsmentioning

confidence: 99%

Allograft tissue under the microscope: only the beginning

Virmani

Rao

Menon

2023

Current Opinion in Organ Transplantation

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Purpose of reviewTo review novel modalities for interrogating a kidney allograft biopsy to complement the current Banff schema.Recent findingsNewer approaches of Artificial Intelligence (AI), Machine Learning (ML), digital pathology including Ex Vivo Microscopy, evaluation of the biopsy gene expression using bulk, single cell, and spatial transcriptomics and spatial proteomics are now available for tissue interrogation.SummaryBanff Schema of classification of allograft histology has standardized reporting of tissue pathology internationally greatly impacting clinical care and research. Inherent sampling error of biopsies, and lack of automated morphometric analysis with ordinal outputs limit its performance in prognostication of allograft health. Over the last decade, there has been an explosion of newer methods of evaluation of allograft tissue under the microscope. Digital pathology along with the application of AI and ML algorithms could revolutionize histopathological analyses. Novel molecular diagnostics such as spatially resolved single cell transcriptomics are identifying newer mechanisms underlying the pathologic diagnosis to delineate pathways of immunological activation, tissue injury, repair, and regeneration in allograft tissues. While these techniques are the future of tissue analysis, costs and complex logistics currently limit their clinical use.

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Section: Spatial Transcriptomicsmentioning

confidence: 99%

Allograft tissue under the microscope: only the beginning

Virmani

Rao

Menon

2023

Current Opinion in Organ Transplantation

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“…MS-based proteomics is a promising approach for SOT biomarker and therapeutic target discovery by providing global profiling and quantitative readout of proteoform changes ( 20 , 100 ). However, current proteomic workflows in SOT research focus on the analysis of bulk clinical samples.…”

Section: Next Frontiers In Proteomics For Advancing Transplant Outcomesmentioning

confidence: 99%

Mass spectrometry-based proteomics for advancing solid organ transplantation research

Huang,

Su,

Fisher

et al. 2023

Front. Transplant.

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Scarcity of high-quality organs, suboptimal organ quality assessment, unsatisfactory pre-implantation procedures, and poor long-term organ and patient survival are the main challenges currently faced by the solid organ transplant (SOT) field. New biomarkers for assessing graft quality pre-implantation, detecting, and predicting graft injury, rejection, dysfunction, and survival are critical to provide clinicians with invaluable prediction tools and guidance for personalized patients' treatment. Additionally, new therapeutic targets are also needed to reduce injury and rejection and improve transplant outcomes. Proteins, which underlie phenotypes, are ideal candidate biomarkers of health and disease statuses and therapeutic targets. A protein can exist in different molecular forms, called proteoforms. As the function of a protein depends on its exact composition, proteoforms can offer a more accurate basis for connection to complex phenotypes than protein from which they derive. Mass spectrometry-based proteomics has been largely used in SOT research for identification of candidate biomarkers and therapeutic intervention targets by so-called “bottom-up” proteomics (BUP). However, such BUP approaches analyze small peptides in lieu of intact proteins and provide incomplete information on the exact molecular composition of the proteins of interest. In contrast, “Top-down” proteomics (TDP), which analyze intact proteins retaining proteoform-level information, have been only recently adopted in transplantation studies and already led to the identification of promising proteoforms as biomarkers for organ rejection and dysfunction. We anticipate that the use of top-down strategies in combination with new technological advancements in single-cell and spatial proteomics could drive future breakthroughs in biomarker and therapeutic target discovery in SOT.

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