Genomic Sequencing in Precision Medicine: Applications, Interpretation and Limitations

Year 2025, Volume: 6 Issue: 2, 71 - 76, 20.05.2025

Marvellous Oyebanjo , Godswill Arinzechukwu Iwuchukwu

https://doi.org/10.47482/acmr.1627345

Abstract

Genomic sequencing (GS) has become a cornerstone in precision medicine (PM), facilitating the identification of genetic variants linked to disease susceptibility, diagnosis, and treatment customization. Leveraging next-generation sequencing technologies, including whole-exome sequencing (WES) and whole-genome sequencing (WGS), GS provides unparalleled insights into genetic underpinnings of rare diseases, cancers, and multifactorial conditions. WES focuses on protein-coding regions, efficiently identifying pathogenic variants, while WGS offers comprehensive genomic coverage, enabling the detection of structural and non-coding variants. Despite its transformative potential, GS faces limitations such as variant interpretation challenges, lack of exhaustive annotation for non-coding regions, and variability in clinical significance assessment. The integration of variant databases like ClinVar and GnomAD, alongside machine learning-driven annotation, has improved variant prioritization and clinical applicability. However, the implementation of GS in clinical practice remains hampered by knowledge gaps among healthcare providers and inconsistencies in defining actionable mutations. Emerging techniques such as spatial transcriptomics and single-cell genomics, coupled with multi-omics data integration, promise to address these challenges, enhancing the precision and utility of GS in PM. This review highlights GS's clinical applications, including early disease risk detection, targeted therapeutics, and oncogenomic advancements, while addressing its interpretive and operational barriers. Future directions emphasize technology innovations and interdisciplinary strategies to maximize GS's clinical impact, positioning it as a critical tool in the era of personalized healthcare.

Keywords

Precision Medicine , Next Generation Sequencing , Rare Diseases , Oncogenomic , Spatial Transcriptomics

Ethical Statement

Ethical approval was not required for this study as it is a review article that does not involve human participants, animals, or sensitive data.

Supporting Institution

This review received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Thanks

There are no acknowledgements.

Hassas Tıpta Genomik Dizileme: Uygulamalar, Yorumlama ve Sınırlamalar

Abstract

Genomik dizileme (GS), hassas tıpta (PM) temel bir taş haline gelerek hastalık duyarlılığı, tanı ve
tedavi özelleştirmesiyle bağlantılı genetik varyantların tanımlanmasını kolaylaştırmaktadır. Tüm
ekzom dizileme (WES) ve tüm genom dizileme (WGS) dahil olmak üzere yeni nesil dizileme
teknolojilerinden yararlanan GS, nadir hastalıkların, kanserlerin ve çok faktörlü durumların
genetik temellerine dair eşsiz içgörüler sağlar. WES, patojenik varyantları etkili bir şekilde
belirleyerek protein kodlayan bölgelere odaklanırken, WGS kapsamlı genomik kapsam sunarak
yapısal ve kodlamayan varyantların tespitini mümkün kılar. Dönüştürücü potansiyeline rağmen
GS, varyant yorumlama zorlukları, kodlamayan bölgeler için kapsamlı açıklama eksikliği ve
klinik önem değerlendirmesinde değişkenlik gibi sınırlamalarla karşı karşıyadır. ClinVar ve
GnomAD gibi varyant veritabanlarının makine öğrenimi odaklı açıklama ile birleştirilmesi,
varyant önceliklendirmesini ve klinik uygulanabilirliği iyileştirmiştir. Ancak, GS'nin klinik
uygulamada uygulanması, sağlık hizmeti sağlayıcıları arasındaki bilgi boşlukları ve eyleme
geçirilebilir mutasyonları tanımlamadaki tutarsızlıklar nedeniyle engellenmeye devam ediyor.
Çoklu omik veri entegrasyonu ile birleştirilmiş mekansal transkriptomik ve tek hücreli genomik
gibi ortaya çıkan teknikler, bu zorlukları ele alarak GS'nin PM'deki hassasiyetini ve faydasını
artırmayı vaat ediyor. Bu inceleme, erken hastalık riski tespiti, hedefli terapötikler ve
onkogenomik ilerlemeler dahil olmak üzere GS'nin klinik uygulamalarını vurgularken,
yorumlayıcı ve operasyonel engellerini de ele alıyor. Gelecekteki yönler, GS'nin klinik etkisini en
üst düzeye çıkarmak için teknoloji yeniliklerini ve disiplinler arası stratejileri vurgulayarak, onu
kişiselleştirilmiş sağlık hizmeti çağında kritik bir araç olarak konumlandırıyor.

Keywords

Hassas Tıp , Yeni Nesil Dizileme , Nadir Hastalıklar , Onkogenomik , Uzaysal Transkriptomik

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