TCM-Mesh: The database and analytical system for network pharmacology analysis for TCM preparations

Abstract

With the advancement of systems biology research, we have already seen great progress in pharmacology studies, especially in network pharmacology. Network pharmacology has been proven to be effective for establishing the "compounds-proteins/genes-diseases" network, and revealing the regulation principles of small molecules in a high-throughput manner, thus would be very effective for the analysis of drug combinations, especially for TCM preparations. In this work, we have proposed the TCM-Mesh system, which records TCM-related information collected from various resources and could serve for network pharmacology analysis for TCM preparations in a high-throughput manner (http://mesh.tcm.microbioinformatics.org/). Currently, the database contains 6,235 herbs, 383,840 compounds, 14,298 genes, 6,204 diseases, 144,723 gene-disease associations, 3,440,231 pairs of gene interactions, 163,221 side effect records and 71 toxic records, and web-based software construct a network between herbs and treated diseases, which will help to understand the underlying mechanisms for TCM preparations at molecular levels. We have used 1,293 FDA-approved drugs, as well as compounds from an herbal material Panax ginseng and a patented drug Liuwei Dihuang Wan (LDW) for evaluating our database. By comparison of different databases, as well as checking against literature, we have demonstrated the completeness, effectiveness, and accuracy of our database.

Figure 1

The network constructed for eight FDA approved drugs. (A) Leucovorin; (B) 5-fluorouracil; (C) Hydrocortisone; (D) Regorafenib; (E) Capecitabine; (F) Sulfasalazine; (G) Prednisone; (H) Oxaliplatin. The innermost node represented the drug, the circle in the middle represented the drug-related genes, the outermost layer represented the gene related diseases. Node: yellow square, compound; blue circle, gene; red triangle, disease. Line: the line between yellow square and blue circle, compound-gene links; the line between blue circle and red triangle, gene-disease associations.

Figure 2

Evaluation of database accuracy based on search results. Different histograms represented top-n genes with the highest combined score of a specific drug used for evaluation; the number in the histogram represented the number of drugs whose top-n genes were related to the indication; percentage represented the ratio of the number in the histogram to the amount of drugs used for evaluation. X axis: top-n genes that were used for evaluation; Y axis: number of the drugs whose related genes were related to the indication of the drug.

Figure 3

The comparison result of TCM-Mesh and TCMID by using compounds of ginseng. The number in the circle represented the amount of compounds that could be retrieved with hits in the databases.

Figure 4

The pharmacology network generated for ginseng. The innermost circle represents the compounds collected from the ginseng, the circle in the middle represented the related genes of compounds from ginseng, the outermost layer represented the diseases that were related to the genes. Node: yellow square, compound; blue circle, gene; red triangle, disease. Line: the line between yellow square and blue circle, compound-gene links; the line between blue circle and red triangle, potential links between gene and disease. The ginseng in the figure was drawn in-house according to the real ginseng.

Figure 5

The pharmacology network generated for LDW. The innermost circle represented the compounds collected from LDW, the circle in the middle represented the related genes of compounds from LDW, the outermost layer represented the diseases that were related to the genes. Node: yellow square, compound; blue circle, gene; red triangle, disease. Line: the line between yellow square and blue circle, compound-gene links; the line between blue circle and red triangle, potential links between gene and disease.

Figure 6

The searching efficiency of the database. (A) Time consumed of the first query and the second query; (B) Time spent on different steps of the whole process; (C) Searching time of searching with different amount of compounds.

Figure 7

The data organization scheme and search pipeline of TCM-Mesh. (A) the source data of the TCM-Mesh, the raw data was consisted of ten data fields; (B) the filtered data of the TCM-Mesh, the filtered data consisted of eight data fields, and the size of data was reduced significantly compared with the previous database shown in (A); (C) the web service provided for TCM-Mesh, compound, protein, gene and disease could be input for searching, threshold of combined score could be set by users to filter the results, network and download functions were available; (D) the results and interpretation showed by TCM-Mesh, which could be use for further analysis. The ginseng in the figure was drawn in-house according to the real ginseng.

Figure 8

The home page and the result page of the web service. (A) the home page of the web of TCM-Mesh, the users could input herb, compound, gene and disease to search with the corresponding results been retrieved. (B) the searching suggestion when searched for ginseng. (C) the result page of the web when searched “ren shen”(ginseng) and the combined score was set to 700, the page showed the basic information of ginseng, the herb ingredients, the toxicity and side effect of compounds that ginseng contained and the ginseng gene-related diseases. (D) The ginseng related gene ADA was searched in the web and its related herbs, compounds, diseases and gene-disease associations were listed on the page. (E) The disease “Diabetes” and the gene “INS” were searched in the web, the INS related disease and the gene-disease associations were shown.