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Biology subjects

Lischer, C.

Publications and source records attributed to Lischer, C..

2 recordsLinked to original sources

An algorithm that combines machine learning ensemble modeling and network analysis to predict self-tolerant tumor-associated antigens for anti-cancer immunotherapy

Tumor-associated antigens (TAAs) and their derived peptides constitute the chance to design off-the-shelf mainline or adjuvant anti-cancer immunotherapies for a broad array of patients. Here, we present a computational pipeline that selects and ranks candidate antigens in a multi-pronged approach and applied it to the case of uveal melanoma. In addition to antigen expression in the tumor target and in healthy tissues, we incorporated a network analysis-derived antigen indispensability index motivated by computational modeling results, and candidate immunogenicity predictions from a machine learning ensemble model on peptide physicochemical characteristics.

bioinformatics↗

Network and systems based re-engineering of dendritic cells with non-coding RNAs forcancer immunotherapy

Dendritic cells (DCs) are professional antigen-presenting cells that induce and regulate adaptive immunity by presenting antigens to T cells. Due to their coordinative role in adaptive immune responses, DCs have been used as cell-based therapeutic vaccination against cancer. The capacity of DCs to induce a therapeutic immune response can be enhanced by re-wiring of cellular signalling pathways with microRNAs (miRNAs). Since the activation and maturation of DCs is controlled by an interconnected signalling network, we deploy an approach that combines RNA sequencing data and systems biology methods to delineate miRNA-based strategies that enhance DC-elicited immune responses. Through RNA sequencing of IKK{beta}-matured DCs that are currently being tested in a clinical trial on therapeutic anti-cancer vaccination, we identified 44 differentially expressed miRNAs. According to a network analysis, most of these miRNAs regulate targets that are linked to immune pathways, such as cytokine and interleukin signalling. We employed a network topology-oriented scoring model to rank the miRNAs, analysed their impact on immunogenic potency of DCs, and identified dozens of promising miRNA candidates with miR-15a and miR-16 as the top ones. The results of our analysis are incorporated in a database which constitutes a tool to identify DC-relevant miRNA-gene interactions with therapeutic potential (www.synmirapy.net/dc-optimization).

systems biology↗