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In September 2021, Zhang Xiaoyan's research group from the School of Life Sciences and Technology of Tongji University published an article ViMIC: a database of human disease-related virus mutations, integration sites and cis in Nucleic Acids Research (JCR Division 1, Chinese Academy of Sciences, IF=16.
971).
-effects, established the virus mutation, integration and cis-effect database ViMIC (http://bmtongji.
cn/ViMIC/index.
php)
.
The pathogenesis of the virus is very complex, involving many aspects of interaction with the host
.
Studies have shown that viruses can exert cis-effects by integrating their genomes into human chromosomes
.
Mutations in viral regions or genes may also increase the risk of disease progression and drug resistance
.
In addition, certain viral mutations may play an important role in promoting the occurrence of diseases by increasing or reducing the incidence of viral DNA integration into host cells
.
At present, there are millions of virus-related studies on PubMed, and there are also relevant databases collecting relevant information, such as virus integration site databases VISDB, Dr.
VIS, RID and ISDB.
However, the existing databases do not contain public resources.
Comprehensive, standardized, and functionally annotated viral mutations and viral integration sites
.
Therefore, how to quickly browse, visualize, and use existing knowledge to study the interaction between the virus and the host is a challenge for researchers
.
So far, the ViMIC database has collected information on 8 viruses (HBV, HPV, EBV, AAV2, MCV, HTLV1, HIV, XMRV) covering 77 human diseases from Pubmed, Cistrome data Browser, VISDB, NCBI Nucleotide and GEO databases.
Including 31,712 viral mutation entries, 105,624 integration sites, 16,310 viral target genes and 1,110,015 viral sequence information
.
At the same time, ViMIC can explore the cis-effects of virus-host interactions through histone modifications, transcription factor binding, and chromatin accessibility at viral integration sites, including 78 histone modifications and 1,358 transcriptional regulatory factors.
The binding site (Table 1)
.
Table 1 ViMIC contains three main modules: virus mutation site, viral integration site and target gene
.
Virus mutation site module includes mutation site annotation and sequence information statistics
.
For each virus mutation site, ViMIC provides annotation information such as mutation level, virus gene/protein/region, virus-related disease, genotype/subtype, whether immune escape/drug resistance, and literature supporting evidence
.
The virus integration site module calculates the overlap number of the virus integration fragment-Cistrome factor, and is used to explore whether the virus integration site participates in a functional region of the host genome
.
For each viral integrated fragment, if there is overlap with Cistrome factor (sum of overlap> 0), ViMIC will give detailed results, including the number of overlaps and the corresponding GSMID, cell line, cell type, tissue type and factor of each Cistrome sample Comment on the name
.
ViMIC uses heat maps and histograms to count the overlap of all viral integration sites and Cistrome factors on human chromosomes
.
The target gene module provides information about the target gene inserted by the virus or affected by the virus gene/protein/region, including gene name, full name, alias, transcript, gene type, gene location information, gene function, gene id, and related drugs.
.
For each gene, ViMIC collects gene expression data of some virus-related disease patients, and can view the relationship between its expression and immune cell infiltration
.
Figure 1 is a schematic overview of the ViMIC database
.
Figure 1 On the home page of the virus mutation interface, the user can view all the currently reported pathogenic mutations of the virus by selecting the number of mutations of any virus of interest, and further select virus genes or diseases to view the virus genes or disease-related mutations
.
Taking HBV as an example, the user can click the green button with the HBV VM number in the virus mutation overview page, as shown in Figure 2A
.
ViMIC will return a table containing information about the HBV mutation site that has been manually proofread
.
Users can screen for mutations by gene/protein/region or disease, enter keywords in the search box at the upper right corner of the form, and click the View button to view the detailed information of the searched mutations
.
In addition, users can click the Sequence button to browse statistics of HBV genome sequences from different regions of the world
.
The virus mutation module will help users get HBV-related progress and quickly find mutations of interest
.
On the homepage of the virus integration interface, suppose the user wants to obtain a detailed list of VIS items, the user can follow the steps in Figure 2B
.
Take the 1000606 entry of HBV chromosome 5 as an example.
After the user clicks on chr5 and searches for the 1000606 entry, ViMIC will display the overlap result of the VIS and the three types of Cistrome factors
.
By clicking the green button with a number in the TFBS (transcription factor binding site) column and filtering the biological source, ViMIC displays the ranking of 16 transcription regulators that overlap with the VIS
.
Then, the user can view the Cistrome samples by clicking the View button of the transcription factor MYC, and they can find that the positions of the three samples on chromosome 5 (coordinates: 1295020, hg38) show the overlap between 1000606 and MYC
.
If users want to observe whether there are mutations in VIS 1000606, they can click the View VIS-VM association button to quickly search for DVID in the Mutation and Sequence panels to obtain related information
.
In addition, users can also select chr5 in the HBV integration menu to view the overlapping distribution of the three factors and virus integration fragments on chromosome 5
.
You can also select the factor browse menu to view all overlapping entries between HBV VIS and MYC (Figure 2B)
.
Since TERT is the target gene of VIS 1000606, on the viral target gene page, ViMIC also provides CIBERSORT-based immune analysis between TERT gene expression and 22 immune cells
.
The detailed information page of TERT shows the heat map and related analysis results of HBV infection diseases and the detailed information of TERT gene.
TERT gene expression analysis results further show that there is a positive correlation trend with CD8+ T cells in HBV+ samples (Figure 2C)
.
Figure 2 ViMIC is a comprehensive resource of human disease-related viruses
.
The database interface is simple and friendly, allowing users to quickly query virus mutations, VIS-Cistrome interactions, virus sequences, VIS-VM correlations in viral infectious diseases, and immune cell infiltration levels, and those affected by integration events or viral genes/regions/proteins.
The correlation of gene expression helps to explore the pathogenic mechanism of viruses
.
The editor is not easy to write, please contact the good-speaking editor butler at 15510012760 (same number on WeChat) for questions related to Shengxin: 18501230653 (same number on WeChat)
971).
-effects, established the virus mutation, integration and cis-effect database ViMIC (http://bmtongji.
cn/ViMIC/index.
php)
.
The pathogenesis of the virus is very complex, involving many aspects of interaction with the host
.
Studies have shown that viruses can exert cis-effects by integrating their genomes into human chromosomes
.
Mutations in viral regions or genes may also increase the risk of disease progression and drug resistance
.
In addition, certain viral mutations may play an important role in promoting the occurrence of diseases by increasing or reducing the incidence of viral DNA integration into host cells
.
At present, there are millions of virus-related studies on PubMed, and there are also relevant databases collecting relevant information, such as virus integration site databases VISDB, Dr.
VIS, RID and ISDB.
However, the existing databases do not contain public resources.
Comprehensive, standardized, and functionally annotated viral mutations and viral integration sites
.
Therefore, how to quickly browse, visualize, and use existing knowledge to study the interaction between the virus and the host is a challenge for researchers
.
So far, the ViMIC database has collected information on 8 viruses (HBV, HPV, EBV, AAV2, MCV, HTLV1, HIV, XMRV) covering 77 human diseases from Pubmed, Cistrome data Browser, VISDB, NCBI Nucleotide and GEO databases.
Including 31,712 viral mutation entries, 105,624 integration sites, 16,310 viral target genes and 1,110,015 viral sequence information
.
At the same time, ViMIC can explore the cis-effects of virus-host interactions through histone modifications, transcription factor binding, and chromatin accessibility at viral integration sites, including 78 histone modifications and 1,358 transcriptional regulatory factors.
The binding site (Table 1)
.
Table 1 ViMIC contains three main modules: virus mutation site, viral integration site and target gene
.
Virus mutation site module includes mutation site annotation and sequence information statistics
.
For each virus mutation site, ViMIC provides annotation information such as mutation level, virus gene/protein/region, virus-related disease, genotype/subtype, whether immune escape/drug resistance, and literature supporting evidence
.
The virus integration site module calculates the overlap number of the virus integration fragment-Cistrome factor, and is used to explore whether the virus integration site participates in a functional region of the host genome
.
For each viral integrated fragment, if there is overlap with Cistrome factor (sum of overlap> 0), ViMIC will give detailed results, including the number of overlaps and the corresponding GSMID, cell line, cell type, tissue type and factor of each Cistrome sample Comment on the name
.
ViMIC uses heat maps and histograms to count the overlap of all viral integration sites and Cistrome factors on human chromosomes
.
The target gene module provides information about the target gene inserted by the virus or affected by the virus gene/protein/region, including gene name, full name, alias, transcript, gene type, gene location information, gene function, gene id, and related drugs.
.
For each gene, ViMIC collects gene expression data of some virus-related disease patients, and can view the relationship between its expression and immune cell infiltration
.
Figure 1 is a schematic overview of the ViMIC database
.
Figure 1 On the home page of the virus mutation interface, the user can view all the currently reported pathogenic mutations of the virus by selecting the number of mutations of any virus of interest, and further select virus genes or diseases to view the virus genes or disease-related mutations
.
Taking HBV as an example, the user can click the green button with the HBV VM number in the virus mutation overview page, as shown in Figure 2A
.
ViMIC will return a table containing information about the HBV mutation site that has been manually proofread
.
Users can screen for mutations by gene/protein/region or disease, enter keywords in the search box at the upper right corner of the form, and click the View button to view the detailed information of the searched mutations
.
In addition, users can click the Sequence button to browse statistics of HBV genome sequences from different regions of the world
.
The virus mutation module will help users get HBV-related progress and quickly find mutations of interest
.
On the homepage of the virus integration interface, suppose the user wants to obtain a detailed list of VIS items, the user can follow the steps in Figure 2B
.
Take the 1000606 entry of HBV chromosome 5 as an example.
After the user clicks on chr5 and searches for the 1000606 entry, ViMIC will display the overlap result of the VIS and the three types of Cistrome factors
.
By clicking the green button with a number in the TFBS (transcription factor binding site) column and filtering the biological source, ViMIC displays the ranking of 16 transcription regulators that overlap with the VIS
.
Then, the user can view the Cistrome samples by clicking the View button of the transcription factor MYC, and they can find that the positions of the three samples on chromosome 5 (coordinates: 1295020, hg38) show the overlap between 1000606 and MYC
.
If users want to observe whether there are mutations in VIS 1000606, they can click the View VIS-VM association button to quickly search for DVID in the Mutation and Sequence panels to obtain related information
.
In addition, users can also select chr5 in the HBV integration menu to view the overlapping distribution of the three factors and virus integration fragments on chromosome 5
.
You can also select the factor browse menu to view all overlapping entries between HBV VIS and MYC (Figure 2B)
.
Since TERT is the target gene of VIS 1000606, on the viral target gene page, ViMIC also provides CIBERSORT-based immune analysis between TERT gene expression and 22 immune cells
.
The detailed information page of TERT shows the heat map and related analysis results of HBV infection diseases and the detailed information of TERT gene.
TERT gene expression analysis results further show that there is a positive correlation trend with CD8+ T cells in HBV+ samples (Figure 2C)
.
Figure 2 ViMIC is a comprehensive resource of human disease-related viruses
.
The database interface is simple and friendly, allowing users to quickly query virus mutations, VIS-Cistrome interactions, virus sequences, VIS-VM correlations in viral infectious diseases, and immune cell infiltration levels, and those affected by integration events or viral genes/regions/proteins.
The correlation of gene expression helps to explore the pathogenic mechanism of viruses
.
The editor is not easy to write, please contact the good-speaking editor butler at 15510012760 (same number on WeChat) for questions related to Shengxin: 18501230653 (same number on WeChat)
