PRESENTATION ABSTRACTS
genome, with outlier peaks harbouring DLA and olfactory receptor genes. To aid functional prioriti- sation, SNVs were annotated with SnpEff and Zoonomia 240 mammal phyloP conservation scores. Benchmarking with OMIA variants showed constrained positions were negatively correlated with allele frequency and prioritised OMIA trait and disease associated variants. While common (allele frequency ‚â•5%) constrained variants may represent genetic positions which allow a population to adapt to its environment, these can also indicate positions underling breed selection. Dog10K data is freely available for community use. #15 Canine Cancer Cell Atlas: A resource to advance interspecies knowledge of the tumor microenvironment Skyler T. Kramer 1 , McKaela A. Hodge 2,3 , Edward Rice 1 , Yulia Innokenteva 4 , Peter J. Dickerson 5 , Jeffrey N. Bryan 6 , Shirley Chu 6 , Heather Wilson-Robles 2 , Shay Bracha 2 , Obi Griffith 6 , Dong Xu 4 , Brian W Davis 2,3 , and Wesley C Warren 1 stk7c9@umsystem.edu 1 Department of Animal Sciences, Department of Surgery, Institute for Data Sciences and Informatics, Bond Life Sciences Center, University of Missouri, Columbia, MO, USA; 2 Department of Small Animal Clinical Science, Texas A&M College of Veterinary Medicine and Biomedical Sciences, College Station, TX, USA; 3 Department of Veterinary Integrative Biosciences Sciences, Texas A&M University, College Station, USA, TX; 4 Institute for Data Sciences and Informatics, Department of Electrical Engineering and Computer Science, University of Missouri, Columbia, MO, USA; 5 Department of Surgical and Radiologi- cal Sciences, School of Veterinary Medicine, University of California-Davis, CA, USA; 6 Department of On- cology, School of Veterinary Medicine, University of Missouri, Columbia, MO, USA; 7 McDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA The use of single cell and nuclei technology has revolutionized our knowledge of the tumor mi- croenvironment (TME) by observing individual cell dynamics, including unresponsive immune cell types, cellular and molecular heterogeneity, and initial primary and progressive metastatic tumor paths. Naturally occurring canine cancers, unlike induced mouse models, continue to offer unique and applicable comparisons to the human TME. Given the rapidly expanding sequencing of canine tumors, we propose a Canine Cancer Cell Atlas consortium effort that tackles the complex task of examining the TME across canine cancer types using the single cell or nuclei RNAseq (sc/ snRNAseq) approach. Sc/snRNAseq data for invasive urothelial cell carcinoma (iUC), osterosar- coma (OS), melanoma, and hepatocellular carcinoma (HCC) have been generated to start this process. In iUC, we document the rarity of cells expressing BRAF, the current gold-standard diag- nostic test, and even fewer possessing the diagnostic V595E mutation. For osteosarcoma, we define a novel immune environment surrounding the tumor site with potential prognostic value. In canine HCC we also define the immune cell landscape but find few molecular signatures shared with non-viral initiated human HCC. Across canine cancer types, we demonstrate variable expression heterogeneity between breeds, as well as between sample sites. Cell typing by clustering, differ- ential expression testing, comparisons to circulating canine immune cells, and to similar human cancer types shows commonalities but more importantly differences, though these vary by cancer type. Our preliminary analyses of these canine cancer types show the immense opportunities to mine these data for therapeutic strategies of canine tumor intervention.
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