Arbitrio Mariamena, Milano Marianna, Lucibello Maria, Altomare Emanuela, Staropoli Nicoletta, Tassone Pierfrancesco, Tagliaferri Pierosandro, Cannataro Mario, Agapito Giuseppe
Institute for Biomedical Research and Innovation, National Research Council, Catanzaro, Italy.
Department of Experimental and Clinical Medicine, University Magna Græcia, Catanzaro, Italy.
Front Pharmacol. 2025 Apr 11;16:1548991. doi: 10.3389/fphar.2025.1548991. eCollection 2025.
The sequencing of the human genome in 2003 marked a transformative shift from a one-size-fits-all approach to personalized medicine, emphasizing patient-specific molecular and physiological characteristics. Advances in sequencing technologies, from Sanger methods to Next-Generation Sequencing (NGS), have generated vast genomic datasets, enabling the development of tailored therapeutic strategies. Pharmacogenomics (PGx) has played a pivotal role in elucidating how the genetic make-up influences inter-individual variability in drug efficacy and toxicity discovering predictive and prognostic biomarkers. However, challenges persist in interpreting polymorphic variants and translating findings into clinical practice. Multi-omics data integration and bioinformatics tools are essential for addressing these complexities, uncovering novel molecular insights, and advancing precision medicine. In this review, starting from our experience in PGx studies performed by DMET microarray platform, we propose a guideline combining machine learning, statistical, and network-based approaches to simplify and better understand complex DMET PGx data analysis which can be adapted for broader PGx applications, fostering accessibility to high-performance bioinformatics, also for non-specialists. Moreover, we describe an example of how bioinformatic tools can be used for a comprehensive integrative analysis which could allow the translation of genetic insights into personalized therapeutic strategies.
2003年人类基因组测序标志着从一刀切的方法向个性化医学的转变,强调患者特异性的分子和生理特征。从桑格测序法到新一代测序(NGS),测序技术的进步产生了大量的基因组数据集,推动了定制治疗策略的发展。药物基因组学(PGx)在阐明基因构成如何影响药物疗效和毒性的个体间差异、发现预测性和预后生物标志物方面发挥了关键作用。然而,在解释多态性变异以及将研究结果转化为临床实践方面仍然存在挑战。多组学数据整合和生物信息学工具对于解决这些复杂性、揭示新的分子见解以及推进精准医学至关重要。在本综述中,基于我们使用DMET微阵列平台进行PGx研究的经验,我们提出了一个结合机器学习、统计学和基于网络的方法的指南,以简化并更好地理解复杂的DMET PGx数据分析,该指南可适用于更广泛的PGx应用,促进包括非专业人员在内的所有人获得高性能生物信息学。此外,我们描述了一个生物信息学工具如何用于全面综合分析的示例,该分析可以将遗传见解转化为个性化治疗策略。