Standing in the canine precision medicine knowledge gap: Improving annotation of canine cancer genomic biomarkers through systematic comparative analysis of human cancer mutations in COSMIC

The accrual of cancer mutation data and related functional and clinical associations have revolutionised human oncology, enabling the advancement of precision medicine and biomarker-guided clinical management. The catalogue of cancer mutations is also growing in canine cancers. However, without direct high-powered functional data in dogs, it remains challenging to interpret and utilise them in research and clinical settings. It is well-recognised that canine and human cancers share genetic, molecular and phenotypic similarities. Therefore, leveraging the massive wealth of human mutation data may help advance canine oncology. Here, we present a structured analysis of sequence conservation and conversion of human mutations to the canine genome through a ‘caninisation’ process. We applied this analysis to COSMIC, the Catalogue of Somatic Mutations in Cancer, the most prominent human cancer mutation database. For the project's initial phase, we focused on the subset of the COSMIC data corresponding to Cancer Gene Census (CGC) genes. A total of 670 canine orthologs were found for 721 CGC genes. In these genes, 365 K unique mutations across 160 tumour types were converted successfully to canine coordinates. We identified shared putative cancer-driving mutations, including pathogenic and hotspot mutations and mutations bearing similar biomarker associations with diagnostic, prognostic and therapeutic utility. Thus, this structured caninisation of human cancer mutations facilitates the interpretation and annotation of canine mutations and helps bridge the knowledge gap to enable canine precision medicine.     

Leading the pack: Best practices in comparative canine cancer genomics to inform human oncology

Pet dogs develop spontaneous cancers at a rate estimated to be five times higher than that of humans, providing a unique opportunity to study disease biology and evaluate novel therapeutic strategies in a model system that possesses an intact immune system and mirrors key aspects of human cancer biology. Despite decades of interest, effective utilization of pet dog cancers has been hindered by a limited repertoire of necessary cellular and molecular reagents for both in vitro and in vivo studies, as well as a dearth of information regarding the genomic landscape of these cancers. Recently, many of these critical gaps have been addressed through the generation of a highly annotated canine reference genome, the creation of several tools necessary for multi-omic analysis of canine tumours, and the development of a centralized repository for key genomic and associated clinical information from canine cancer patients, the Integrated Canine Data Commons. Together, these advances have catalysed multidisciplinary efforts designed to integrate the study of pet dog cancers more effectively into the translational continuum, with the ultimate goal of improving human outcomes. The current review summarizes this recent progress and provides a guide to resources and tools available for comparative study of pet dog cancers.     

竹子光合作用研究进展

介绍了在竹子光合作用方面已进行过研究的主要竹种；总结了已研究竹种光合作用的规律和基本特征，分别阐述了不同生长环境和生理生态因子对竹种光合作用的影响；介绍和讨论了植物光合作用研究的最新手段、方法和趋势；提出了竹子光合作用研究的新思路。着重阐述了竹子光合作用进一步深入研究的首要内容及应采取的研究方法，展望了竹子光合作用研究的蛋白组学方法和功能基因组学方法，以及应用于生产实践的前景。     

Genome-wide genetic dissection of germplasm resources and implications for breeding by design in soybean

“Breeding by Design” as a concept described by Peleman and van der Voort aims to bring together superior alleles for all genes of agronomic importance from potential genetic resources. This might be achievable through high-resolution allele detection based on precise QTL (quantitative trait locus/loci) mapping of potential parental resources. The present paper reviews the works at the Chinese National Center for Soybean Improvement (NCSI) on exploration of QTL and their superior alleles of agronomic traits for genetic dissection of germplasm resources in soybeans towards practicing “Breeding by Design”. Among the major germplasm resources, i.e. released commercial cultivar (RC), farmers’ landrace (LR) and annual wild soybean accession (WS), the RC was recognized as the primary potential adapted parental sources, with a great number of new alleles (45.9%) having emerged and accumulated during the 90 years’ scientific breeding processes. A mapping strategy, i.e. a full model procedure (including additive (A), epistasis (AA), A × environment (E) and AA × E effects), scanning with QTLNetwork2.0 and followed by verification with other procedures, was suggested and used for the experimental data when the underlying genetic model was usually unknown. In total, 110 data sets of 81 agronomically important traits were analyzed for their QTL, with 14.5% of the data sets showing major QTL (contribution rate more than 10.0% for each QTL), 55.5% showing a few major QTL but more small QTL, and 30.0% having only small QTL. In addition to the detected QTL, the collective unmapped minor QTL sometimes accounted for more than 50% of the genetic variation in a number of traits. Integrated with linkage mapping, association mappings were conducted on germplasm populations and validated to be able to provide complete information on multiple QTL and their multiple alleles. Accordingly, the QTL and their alleles of agronomic traits for large samples of RC, LR and WS were identified and then the QTL-allele matrices were established. Based on which the parental materials can be chosen for complementary recombination among loci and alleles to make the crossing plans genetically optimized. This approach has provided a way towards breeding by design, but the accuracy will depend on the precision of the loci and allele matrices.     

林木遗传育种基础研究热点述评

林木由于世代周期长、个体高大、遗传负荷高等自身固有的一些特性,一直被认为是一种非常难以操作的遗传学材料,导致林木遗传育种在基础研究方面远远滞后于模式动、植物和其他重要作物,成为限制林木遗传改良进程的主要因素。分子育种是突破林木育种周期长的关键技术,通过基因组学研究,分析和阐明林木基因的功能是进行林木分子育种设计的前提。近年来随着生命科学领域新技术的快速发展,林木遗传育种基础研究也出现一些新的热点。本文主要阐述林木基因组和功能基因组学、连锁与关联分析、木材形成机制及分子育种技术的研究进展,虽然目前相关研究成果实际应用的条件还不成熟,但作为技术储备是急需加强的研究方向。     

RNA干扰技术及其应用研究

RNA干涉作用,是生物界一种古老而且进化上高度保守的现象,是基因转录后沉默作用(PTGS)的重要机制之一.它能定向关闭生物体内某一基因,使其不发挥作用,同时不影响其他基因的功能,便于研究特定基因的功能.在后基因组时代的基因功能研究、基因治疗和药物开发中具有广阔的应用前景.     

功能基因组学的研究方法

基因组学研究已经由以全基因组测序为目标的结构基因组学转向以基因功能鉴定为目标的功能基因组学研究。作者综述了功能基因组学的内容、主要的新方法和新技术，如SAGE、ESTs、SSH、微阵列、生物信息学、RNAi等，并对其发展进行了简单展望。     

蛋白质组学及其在奶牛乳房炎研究中的应用

蛋白质组学是功能基因组学的重要组成部分,已被广泛应用于人类疾病等相关研究领域。二维凝胶电泳、质谱和生物信息学是蛋白质组学研究的三大关键技术。文章概述了蛋白质组学研究技术的最新进展和白细胞蛋白质组学、微生物蛋白质组学、差异蛋白质组学的研究进展,以及蛋白质组学在奶牛乳房炎发病机理、诊断和防治等相关研究中的应用与前景。     

生物信息学研究进展

随着计算机科学和生物科学的迅猛发展,由此而诞生的生物信息学逐渐发展成为一门独立的学科。它将会成为21世纪生命科学中的重要研究领域之一。本文简单介绍了生物信息学的产生,发展,研究内容,应用及未来的发展方向等。     

犬基因组研究进展

人类基因组计划逐渐发展成熟使比较基因组学研究成为必然。犬由于具有遗传多样性和疾病易感性等特点,是一个极好的比较基因组学的动物模型。在此,综述了犬基因图谱、基因组测序、犬基因组比较图谱及犬基因组研究应用等方面的研究进展,并提出目前研究中面临的问题。