Browsing by Author "Rosenberg, Avi Z."

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    FUSION: A web-based application for in-depth exploration of multi-omics data with brightfield histology
    (bioRxiv, 2024-08-22) Border, Samuel; Ferreira, Ricardo Melo; Lucarelli, Nicholas; Manthey, David; Kumar, Suhas; Paul, Anindya; Mimar, Sayat; Naglah, Ahmed; Cheng, Ying-Hua; Barisoni, Laura; Ray, Jessica; Strekalova, Yulia; Rosenberg, Avi Z.; Tomaszewski, John E.; Hodgin, Jeffrey B.; HuBMAP consortium; El-Achkar, Tarek M.; Jain, Sanjay; Eadon, Michael T.; Sarder, Pinaki; Medicine, School of Medicine
    Spatial -OMICS technologies facilitate the interrogation of molecular profiles in the context of the underlying histopathology and tissue microenvironment. Paired analysis of histopathology and molecular data can provide pathologists with otherwise unobtainable insights into biological mechanisms. To connect the disparate molecular and histopathologic features into a single workspace, we developed FUSION (Functional Unit State IdentificatiON in WSIs [Whole Slide Images]), a web-based tool that provides users with a broad array of visualization and analytical tools including deep learning-based algorithms for in-depth interrogation of spatial -OMICS datasets and their associated high-resolution histology images. FUSION enables end-to-end analysis of functional tissue units (FTUs), automatically aggregating underlying molecular data to provide a histopathology-based medium for analyzing healthy and altered cell states and driving new discoveries using "pathomic" features. We demonstrate FUSION using 10x Visium spatial transcriptomics (ST) data from both formalin-fixed paraffin embedded (FFPE) and frozen prepared datasets consisting of healthy and diseased tissue. Through several use-cases, we demonstrate how users can identify spatial linkages between quantitative pathomics, qualitative image characteristics, and spatial --omics.
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    Uromodulin to Osteopontin Ratio in Deceased Donor Urine Is Associated With Kidney Graft Outcomes
    (Wolters Kluwer, 2021) Mansour, Sherry G.; Liu, Caroline; Jia, Yaqi; Reese, Peter P.; Hall, Isaac E.; El-Achkar, Tarek M.; LaFavers, Kaice A.; Obeid, Wassim; Rosenberg, Avi Z.; Daneshpajouhnejad, Parnaz; Doshi, Mona D.; Akalin, Enver; Bromberg, Jonathan S.; Harhay, Meera N.; Mohan, Sumit; Muthukumar, Thangamani; Schröppel, Bernd; Singh, Pooja; El-Khoury, Joe M.; Weng, Francis L.; Thiessen-Philbrook, Heather R.; Parikh, Chirag R.; Medicine, School of Medicine
    Background: Deceased-donor kidneys experience extensive injury, activating adaptive and maladaptive pathways therefore impacting graft function. We evaluated urinary donor uromodulin (UMOD) and osteopontin (OPN) in recipient graft outcomes. Methods: Primary outcomes: all-cause graft failure (GF) and death-censored GF (dcGF). Secondary outcomes: delayed graft function (DGF) and 6-month estimated glomerular filtration rate (eGFR). We randomly divided our cohort of deceased donors and recipients into training and test datasets. We internally validated associations between donor urine UMOD and OPN at time of procurement, with our primary outcomes. The direction of association between biomarkers and GF contrasted. Subsequently, we evaluated UMOD:OPN ratio with all outcomes. To understand these mechanisms, we examined the effect of UMOD on expression of major histocompatibility complex II in mouse macrophages. Results: Doubling of UMOD increased dcGF risk (adjusted hazard ratio [aHR], 1.1; 95% confidence interval [CI], 1.02-1.2), whereas OPN decreased dcGF risk (aHR, 0.94; 95% CI, 0.88-1). UMOD:OPN ratio ≤3 strengthened the association, with reduced dcGF risk (aHR, 0.57; 0.41-0.80) with similar associations for GF, and in the test dataset. A ratio ≤3 was also associated with lower DGF (aOR, 0.73; 95% CI, 0.60-0.89) and higher 6-month eGFR (adjusted β coefficient, 3.19; 95% CI, 1.28-5.11). UMOD increased major histocompatibility complex II expression elucidating a possible mechanism behind UMOD's association with GF. Conclusions: UMOD:OPN ratio ≤3 was protective, with lower risk of DGF, higher 6-month eGFR, and improved graft survival. This ratio may supplement existing strategies for evaluating kidney quality and allocation decisions regarding deceased-donor kidney transplantation.