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Due to the explosion of cancer genome data and the urgent needs for cancer treatment, it is becoming increasingly important and necessary to easily and timely analyze and annotate cancer genomes. However, tumor heterogeneity is recognized as a serious barrier to annotate cancer genomes at the individual patient level. In addition, the interpretation and analysis of cancer multi-omics data rely heavily on existing database resources that are often located in different data centers or research institutions, which poses a huge challenge for data parsing. Here we present CCAS (Cancer genome Consensus Annotation System, https://ngdc.cncb.ac.cn/ccas/#/home), a one-stop and comprehensive annotation system for the individual patient at multi-omics level. CCAS integrates 20 widely recognized resources in the field to support data annotation of 10 categories of cancers covering 395 subtypes. Data from each resource are manually curated and standardized by using ontology frameworks. CCAS accepts data on single nucleotide variant/insertion or deletion, expression, copy number variation, and methylation level as input files to build a consensus annotation. Outputs are arranged in the forms of tables or figures and can be searched, sorted, and downloaded. Expanded panels with additional information are used for conciseness, and most figures are interactive to show additional information. Moreover, CCAS offers multidimensional annotation information, including mutation signature pattern, gene set enrichment analysis, pathways and clinical trial related information. These are helpful for intuitively understanding the molecular mechanisms of tumors and discovering key functional genes.

The Illumina HumanMethylation BeadChip is one of the most cost-effective methods to quantify DNA methylation levels at single-base resolution across the human genome, which makes it a routine platform for epigenome-wide association studies. It has accumulated tens of thousands of DNA methylation array samples in public databases, providing great support for data integration and further analysis. However, the majority of public DNA methylation data are deposited as processed data without background probes which are widely used in data normalization. Here, we present Gaussian mixture quantile normalization (GMQN), a reference based method for correcting batch effects as well as probe bias in the HumanMethylation BeadChip. Availability and implementation: https://github.com/MengweiLi-project/gmqn.

Aeromonas veronii. a ubiquitous of zoonotic disease pathogen, depends on adhesion as the crucial way to colonize the gastrointestinal tract of humans and animals, which further causes severe gastrointestinal diseases and parenteral infections. However, the adherence mechanism of A. veronii has not been fully characterized. Therefore, we investigate the effect of autoinducer-2 (AI-2) on adherence of A. veronii through facilitating the expression of mannose-sensitive hemagglutinin (MSHA) type IV pili genes mediated by cyclic diguanosine monophosphate (c-di-GMP). The deficiency of AI-2 significantly lowered the adherence of A. veronii to erythrocytes and intestinal mucus, and the complement of AI-2 could increase its adherence ability. The deficiency of AI-2 only limited the formation of pili, instead of outer-membrane proteins and lipopolysaccharide, through reducing the expression levels of MSHA type IV pili genes due to the decline of c-di-GMP. The addition of guanosine triphosphate (GTP) could increase the content of c-di-GMP and the expression of MSHA type IV pili genes, and further promote adherence of A. veronii. Therefore, this study reveals, for the first time, adherence mediated by c-di-GMP with MshE as the c-di-GMP receptor is positively regulated by AI-2 in A. veronii, which increases the understanding of colonization strategy of pathogen and may facilitate control of A. veronii infection to host. IMPORTANCE Aeromonas veronii can adhere to host cells through different adherence factors including outer-membrane proteins (OMPs), lipopolysaccharide (LPS), and pili, but its adherence mechanisms are still unclear. Here, we evaluated the effect of autoinducer-2 (AI-2) on adherence of A. veronii and its regulation mechanism. After determination of the promotion effect of AI-2 on adherence, we investigated which adherence factor was regulated by AI-2, and the results show that AI-2 only limits the formation of pili. Among the four distinct pili systems, only the mannose-sensitive hemagglutinin (MSHA) type IV pili genes were significantly downregulated after deficiency of AI-2. MshE, an ATPase belonged to MSHA type IV pilin, was confirmed as c-di-GMP receptor, that can bind with c-di-GMP which is positively regulated by AI-2, and the increase of c-di-GMP can promote the expression of MSHA type IV pili genes and adherence of A. veronii. Therefore, this study confirms that c-di-GMP positively regulated by AI-2 binds with MshE, then increases the expression of MSHA pili genes, finally promoting adherence of A. veronii, suggesting a multilevel positive regulatory adhesion mechanism that is responsible for A. veronii adherence. [ABSTRACT FROM AUTHOR]