Input into cTCrosstalk

Completed at Sat Apr 30 00:15:43 2022 (Asia/Shanghai), with the runtime of 151 seconds on the server side (not including the runtime on the client/user side).

An interactive table of user-input SNPs, with 1st column SNPs for dbSNP rsIDs, 2nd column P-values for significance info.

Output: target genes

Manhattan plot illustrates priority rating for target genes that are color-coded by chromosomes, with the top 30 target genes labelled. Also provided is an editable PDF file for download.

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Manhattan plot illustrating priority rating (y-axis) for target genes (color-coded by chromosomes; x-axis), with top target genes labelled.

Figure 1: Manhattan plot illustrating priority rating (y-axis) for target genes (color-coded by chromosomes; x-axis), with top target genes labelled.

Prioritisation table for targets at the gene level, each receiving 5-star priority rating (scored 0-5; see the column Rating) and its rank (see the column Rank). The prioritised target genes are cross-referenced and hyperlinked to GeneCards; see the column Genes. The column Type tells the target gene type (either Core for core genes or Peripheral for peripheral genes). Also provided is a summary of evidence used to define core genes, including columns Proximity (evidence of genomic proximity), QTL (e/pQTL evidence) and PCHiC (conformation evidence). For details on evidence, please refer to Evidence table.

Evidence table for core genes, showing which SNPs (see the column SNPs) are used to define core genes (the column Core genes) based on which evidence (see the column Evidence). The column SNP type tells the SNP type (either Input for use-input SNPs or LD for LD SNPs). Notably, the column Evidence details datasets used: the prefix Proximity_ indicative of SNPs in the proximity, the prefix PCHiC_ for PCHi-C datasets, and the prefix QTL_ for e/pQTL datasets.

Output: target pathways

A dot plot for target pathways that are prioritised based on pathway enrichment analysis of the top 1% prioritised target genes. Pathways are sourced from the KEGG database (release 101.0). Also provided is an editable PDF file for download.

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Enriched/prioritised pathways based on the top prioritised target genes.

Figure 2: Enriched/prioritised pathways based on the top prioritised target genes.

Prioritisation table for target pathways. Each prioritised pathway (the column Pathways) of belonging KEGG category (the column Category) has the enrichment z-score (the column Z-score), the enrichment significant level (the column FDR), the number of member genes (the column Num) and the member list (the column Members)

Output: targets at the crosstalk level

A network visualisation of pathway crosstalk, with genes/nodes color-coded by priority rating and labelled in the form of rating®rank. The significance (p-value) of observing the identified crosstalk by chance is 5.7e-65, as estimated by a degree-preserving node permutation test. Pathways are sourced from the KEGG database (release 101.0). Also provided is an editable PDF file for download.

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The crosstalk between pathways. Genes/nodes are color-coded by priority rating and labelled in the form of `rating®rank`, while interactions/edges are defined by KEGG pathways.

Figure 3: The crosstalk between pathways. Genes/nodes are color-coded by priority rating and labelled in the form of rating®rank, while interactions/edges are defined by KEGG pathways.

Prioritisation table for pathway crosstalk genes, with the column Rating for priority rating and the column Rank for the priority rank. The crosstalk genes (the column Crosstalk genes) are cross-referenced and hyperlinked to GeneCards. Also provided is a summary of evidence, including columns Proximity (evidence of genomic proximity), QTL (e/pQTL evidence) and PCHiC (conformation evidence). For details on evidence, please refere to Evidence table.

Evidence table for pathway crosstalk genes, showing which SNPs (see the column SNPs) are used to crosstalk genes (the column Crosstalk genes) based on which evidence (see the column Evidence). The column SNP type tells the SNP type (either Input for use-input SNPs or LD for LD SNPs). Notably, the column Evidence details datasets used: the prefix Proximity_ indicative of SNPs in the proximity, the prefix PCHiC_ for PCHi-C datasets, and the prefix QTL_ for e/pQTL datasets.

Output: crosstalk-based drug repurposing

A heatmap-like illustration showing drug repurposing analysis of approved drugs (licensed medications) based on pathway crosstalk genes, with crosstalk genes on y-axis, disease indications on x-axis, red dots indexed in number and referenced beneath in the table where the information on approved drugs and mechanisms of action is detailed. The information on current approved therapeutics is sourced from the ChEMBL database (version 30). Also provided is an editable PDF file for download.

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Drug repurposing analysis of approved drugs (licensed medications) based on pathway crosstalk genes. The heatmap shows crosstalk genes (y-axis) and disease indications (x-axis), with red dots indexed in number and referenced beneath within the table where the information on approved drugs and mechanisms of action is also listed.

Figure 4: Drug repurposing analysis of approved drugs (licensed medications) based on pathway crosstalk genes. The heatmap shows crosstalk genes (y-axis) and disease indications (x-axis), with red dots indexed in number and referenced beneath within the table where the information on approved drugs and mechanisms of action is also listed.

An interactive table of crosstalk genes (the column Crosstalk genes), disease indications (the column Disease indications), approved drugs and mechanisms (the column Approved drugs [mechanisms of action]), and drug index (the column Index) shown above within the dot plot. The crosstalk genes are cross-referenced and hyperlinked to GeneCards.