IMPACT: A web server for exploring immunotherapeutic predictive and cancer prognostic biomarkers

Abstract

Dear Editor,Identifying reliable biomarkers for immune checkpoint inhibitors (ICIs) can efficiently screen beneficiaries to improve their clinical use. We developed a public web server, IMPACT, to facilitate the comprehensive investigation of predictive or prognostic biomarkers, interaction effects and biological mechanisms with both public and inhouse datasets (http://www.brimpact.cn/ or http://impact. brbiotech.com/) (Figure 1A).ICIs have heralded a new era in cancer treatment, while most ICI biomarkers have low generalisation performance due to limited data and statistical methods. Currently, several public database-based tools are available to explore potential biomarkers, such as CAMOIP, 1 Cancer-Immu, 2 CRI-iAtlas 3 and cBioPortal. 4 Compared with these tools (Figure 1B and Table S1), IMPACT uniquely allows users to define customised biomarkers by selecting mutation variant types and automatically screening cut-points for continuous biomarkers and any mutation or co-mutation in a gene set and to conduct more rigorous key analyses including customised multivariable, subgroup and interaction analyses in more datasets (Table S2). Here, we illustrate how to use IMPACT to comprehensively explore biomarkers.Users can start by understanding the general performance of a biomarker using PredExplore and ProgExplore modules to analyse the association between gene alteration and survival across all the ICI and non-ICI datasets. Detailed results in each dataset and forest plot of metaanalysis can be automatically generated. Especially, these modules allow users to automatically explore a predictive or prognostic value of any mutation or co-mutation in a gene set. As a case of DNA damage response (DDR) pathway alteration (Figures 2A,B and S1A,B), the results suggest that pathway mutation could accumulate the minimal effect of single DDR gene mutation to observe a significant association with prolonged survival to ICIs. Comutation is usually used to explore synergistic or mutually exclusive effects between genes. The co-mutation analysisThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Exploring SLC16A1 as an Oncogenic Regulator and Therapeutic Target in Cholangiocarcinoma

“…Subsequently, based on the ssGSEA algorithm, we calculated the level of immune cell infiltration in the TCGA-CHOL cohort using 24 types of immune cell markers provided in the literature. Additionally, we employed the IMPACT online database to analyze differences in immune-related and cancer-related signaling pathway activities between the high and low SLC16A1 expression groups 15 .…”