Artificial Intelligence and Complex Network Approaches Reveal Potential Gene Biomarkers for Hepatocellular Carcinoma

Author:

Lacalamita Antonio12ORCID,Serino Grazia3ORCID,Pantaleo Ester12ORCID,Monaco Alfonso12ORCID,Amoroso Nicola24ORCID,Bellantuono Loredana25ORCID,Piccinno Emanuele3ORCID,Scalavino Viviana3ORCID,Dituri Francesco3,Tangaro Sabina26ORCID,Bellotti Roberto12,Giannelli Gianluigi3ORCID

Affiliation:

1. Dipartimento Interateneo di Fisica M. Merlin, Università degli Studi di Bari Aldo Moro, Via G. Amendola 173, 70125 Bari, Italy

2. Sezione di Bari, Istituto Nazionale di Fisica Nucleare (INFN), Via A. Orabona 4, 70125 Bari, Italy

3. National Institute of Gastroenterology S. De Bellis, IRCCS Research Hospital, Via Turi 27, 70013 Castellana Grotte, BA, Italy

4. Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo Moro, Via A. Orabona 4, 70125 Bari, Italy

5. Dipartimento di Biomedicina Traslazionale e Neuroscienze (DiBraiN), Università degli Studi di Bari Aldo Moro, Piazza G. Cesare 11, 70124 Bari, Italy

6. Dipartimento di Scienze del Suolo, della Pianta e degli Alimenti, Università degli Studi di Bari Aldo Moro, Via G. Amendola 165/a, 70126 Bari, Italy

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the number of cases is constantly increasing. Early and accurate HCC diagnosis is crucial to improving the effectiveness of treatment. The aim of the study is to develop a supervised learning framework based on hierarchical community detection and artificial intelligence in order to classify patients and controls using publicly available microarray data. With our methodology, we identified 20 gene communities that discriminated between healthy and cancerous samples, with an accuracy exceeding 90%. We validated the performance of these communities on an independent dataset, and with two of them, we reached an accuracy exceeding 80%. Then, we focused on two communities, selected because they were enriched with relevant biological functions, and on these we applied an explainable artificial intelligence (XAI) approach to analyze the contribution of each gene to the classification task. In conclusion, the proposed framework provides an effective methodological and quantitative tool helping to find gene communities, which may uncover pivotal mechanisms responsible for HCC and thus discover new biomarkers.

Funder

Italian Ministry of Health

National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.4-Call

Italian Ministry of University and Research funded by the European Union–NextGenerationEU

Concession Decree

Italian Ministry of University and Research

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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