A Multi-disciplinary Approach to Investigating Canine Diffuse Large B cell Lymphoma

研究犬弥漫性大 B 细胞淋巴瘤的多学科方法

• 批准号: 2726000
• 金额: --
• 依托单位: Royal Veterinary College
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2726000
• 关键词: Multi; disciplinary; Approach; Investigating; Canine

RATIONALE: In humans, DLBCL has been shown to demonstrate genetic heterogeneity and miRNA profiles predicting disease prognosis. In dogs there are limited studies and relatively little genetic characterisation of lymphoma, meaning that it is difficult to find correlation with the human disease. Nevertheless, in both humans and dogs, there is a significant subset of lymphomas that are refractory to treatment. OVERALL AIM: We propose to better define genetic subtypes of canine lymphoma and characterising response to treatment of the different subtypes through a combination of more accurate phenotyping of lymphomas by integrating a) advanced image analysis b) genome sequencing, and c) total RNA sequencing (including micro-RNA sequencing).HYPOTHESIS: Canine lymphoma can be more accurately diagnosed, treated and prognosticated through a synergistic molecular, genetics, and image based analysis.SPECIFIC PROJECT OBJECTIVESOBJECTIVE 1: Define morphometric characteristics of canine lymphoma through image analysis of digital whole slide images (WSIs) via machine learning and artificial intelligence methodsOBJECTIVE 2: Identify genetic markers for DLBCL susceptibility through genome wide association studies and CNV analysesOBJECTIVE 3: Define mRNA and miRNA expression profiles in canine DLBCL through mRNAseq and small RNA-seq, and investigate if tumour-associated miRNA can be detected in peripheral blood serumOBJECTIVE 4: Genetic and morphological signatures from 1-3 will be compared between cases that show good response to chemotherapy and those that are refractory to treatment.

理由：在人类中，DLBCL已被证明可以证明遗传异质性和miRNA谱预测疾病预后。在狗中，研究有限，淋巴瘤的遗传表征相对较少，这意味着很难找到与人类疾病的相关性。然而，在人类和狗中，都有很大的淋巴瘤子集对治疗难治性。总体目的：我们建议通过整合a）先进的图像分析b）基因组测序（C）总RNA测序来更好地定义犬淋巴瘤的遗传亚型，并通过更准确的淋巴瘤表型来表征对不同亚型治疗的反应（C）总RNA测序（包括微-RNA测序）。假设：可以通过协同的分子，遗传学和基于图像的分析来更准确地诊断，处理和预测犬通过机器学习和人工智能方法的图像（WSI）2：通过基因组广泛关联研究和CNV AllyseSeSeSeSemeSeSemeSemessive 3：定义DLBCL的遗传标记3：定义MRNASEQ和小RNA-seq中的犬DLBCL中的mRNA和miRNA表达谱，并研究是否肿瘤，并研究肿瘤是否肿瘤 - 可以在外周血血清主体4：在对化学疗法表现出良好反应的病例和对治疗难治的病例之间比较遗传和形态学的相关miRNA。