Unraveling the Molecular Mechanisms of Complex Diseases Using Systems Biology Approach

QC 2024-10-01

Abstract

In the context of rising global health challenges, the mechanistic investigation and

treatment of complex diseases, including cancer, liver diseases, has emerged as a

vital focus in scientific research. A thorough understanding of basic biological

processes is crucial for the development of tools that aid in diagnosing, monitoring,

and treating human diseases. This doctoral thesis investigates the molecular

mechanisms underlying complex human diseases, with an emphasis on discovering

novel therapeutic targets and compounds though systems biology approaches. By

leveraging large-scale transcriptomic data, this work aims to uncover novel insights

into disease biology that can drive drug repositioning and precision medicine. The

thesis integrates various computational strategies and biological frameworks to

connect gene expression patterns with disease progression and therapeutic

opportunities, focusing primarily on cancer and metabolic disorders.

The studies compiled in this thesis contribute to the understanding of human disease

biology through the systematic analysis of gene expression profiles and the

application of network-based methodologies. Paper I introduces the Human

Pathology Atlas, providing an in-depth analysis of gene expression prognostic

features across different cancer types, which improves our understanding of

relationships between gene expression and disease outcomes. Paper II and Paper

III employ gene co-expression network analysis combined with drug repositioning

strategies, identifying promising therapeutic candidates for hepatocellular

carcinoma and pancreatic ductal adenocarcinoma, respectively. These studies

illustrate how network-based approaches can locate key molecular targets and

potential repurposable drugs for various cancer types.

In Paper IV, we apply a network-based approach to investigate the dysregulated

transcriptional regulation in non-alcoholic fatty liver disease (NAFLD). This study

identifies critical genes and pathways involved in the disease progression, providing

new insights into the pathophysiology of NAFLD. Lastly, Paper V presents

comprehensive review on the emerging role of PKLR in liver diseases, highlighting

its connection to metabolic diseases. This review discusses PKLR’s potential as a

therapeutic target, providing a foundation for future studies in metabolic disease

research.

In summary, this thesis contributes to the field of systems biology by integrating

gene expression and network methodologies, offering innovative strategies for

therapeutic development and personalized medicine across complex diseases.

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