1. Introduction

Previous studies have illustrated the important roles of TCMs in immune regulation and proposes a promising future for them in cancer immuno-therapies. In this work, we collected the IO targets and their small molecule ligands, those ligands information were further mapped with the chemical ingredients of the TCM. All those collected data were deposited in web-based publicly accessible database TCMIO, cheminformatics and bioinformatics tools were integrated into this database for user customer analysis.

2. Architecture of TCMIO

TCMIO was implemented into a web-based publicly accessible database, which can be accessed through major web browser. Beego, an open source framework for rapid web development in Golang, used as backend services. RESTful APIs are provided in TCMIO. All data were stored in open source relational database PostgreSQL (version 10.5). The ChemDoodle web component is used for chemical structure visualization. Bingo is used as molecular search cartridge, owning to the state-of-the-art indexing algorithms within the underlying database server, and its supports for high performance similarity, substructure, and full structure searches functions. In order to investigate the mechanism of actions of TCM, Gene enrichment analysis tools were integrated into TCMIO. The Database for Annotation, Visualization and Integrated Discovery (DAVID) is integrated into TCMIO.

3. Tools used in TCMIO

Tools	Purpose	Link
Chinese Pharmacopoeia(2015)	Pharmacopoeia(2015) prescriptions and TCM data source	wp.chp.org.cn/front/chpint/en
UniProt	IO taregts information	www.uniprot.org
ChEMBL 24	IO targets and ligands	www.ebi.ac.uk/chembl
KEGG	pathways data source	www.kegg.jp
TCMAnalyzer	ingredients of TCM	www.rcdd.org.cn/tcmanalyzer
TCMSP	ingredients of TCM	lsp.nwsuaf.edu.cn/tcmsp.php
TCMID	ingredients of TCM	www.megabionet.org/tcmid
DAVID	go enrichment analysis	david.ncifcrf.gov
ipmDraw	structure draw	ipmdraw.iprexmed.com
ChemDoodle Web	structure display of natural products	web.chemdoodle.com
Vis.js	network display	visjs.org
PostgreSQL	storage database	www.postgresql.org
Golang	web server language	golang.org
JQuery	foreground and background interaction	jquery.com

4. Functions

TCMIO contains three functional parts, Browse, Structure, and MOA. Browse page provides information on prescription, TCM, ingredient, target, and ligand libraries. Interactive tables with sorting and searching functions are provided for user to access the data conveniently. Structure page provides cheminformatics tools to accessed the ingredient and ligand libraries which contains the chemical structure data. MOA page provides the bioinformatics tools, concluding network and pathway analysis, to elucidating the mechanism of actions of TCM or prescription.

4.1 Browse

TCMIO contains prescription, TCM, ingredient, target, and ligand libraries. In Browse page, user can browse all the data entries with an interactive table. Server-side processing in DataTables is used, which provides powerful browsing, searching and sorting ability, which help user to access the data of interest efficiently. Searching function supports multi-columns. When user input the search words, server would search multiple columns of current library, and return the results with paging.

4.2 Structure

In Structure page, user could search against ligand and ingredient library using structure search methods, which contains full-structure, sub-structure, and similarity search. There are 5 steps for user to submit a structure search. Step 1: Draw a query structure, or upload structure file using ipmDraw. Step 2: Select a library, ingredient or ligand. Step 3: Select a structure search method. Step 4: Select a similarity threshold. This is only for similarity search. Step 5: Click Search button. Structure search against ingredient library, user could identify all the TCMs which contains the specific chemical structure or similar ingredients with the query structure. Structure search against ligand library, user could identify all ligand hits and their targets with bioactivity data.

4.3 MOA

In MOA page, user could submit TCMs or Prescription with different name types. TCMIO would construct a TCM-ingredient-target network automatically. User could identify the high degree ingredients and targets in the network. The high degree for ingredient suggesting the ingredient could interact with multiple targets, and the high degree for target indicating the target could be targeted by multiple ingredients. This network could conveniently elucidate the mechanism of action for TCM or prescription. Moreover, those targets could be subsequently submitted the DAVID web server for pathway enrichment analysis.

5. Download

All data in TCMIO could be downloaded from Download page.