Special Feature: Genomics for Future Medicine
It has been widely accepted that genome analysis has great potential to explain the causes of diseases and to eventually increase our quality of life. However, the current success is only the first step to achieving genuine future genome medicine. More evidence is still needed to support the clinical translation of the genomics studies. To overcome current hurdles and move one step toward the next generation of precision medicine, more research and evidence will be required. In this special issue of EMM, we present a collection of review articles on cutting edge topics in genomics and genome medicine.
Showing which genes are expressed, or switched on, in individual cells may help to reveal the first signs of disease. Each cell in an organism contains the same genetic information, but cell type and behavior depend on which genes are expressed. Previously, researchers could only sequence cells in batches, averaging the results, but technological improvements now allow sequencing of the genes expressed in an individual cell, known as single-cell RNA sequencing (scRNA-seq). Ji Hyun Lee (Kyung Hee University, Seoul) and Duhee Bang and Byungjin Hwang (Yonsei University, Seoul) have reviewed the available scRNA-seq technologies and the strategies available to analyze the large quantities of data produced. They conclude that scRNA-seq will impact both basic and medical science, from illuminating drug resistance in cancer to revealing the complex pathways of cell differentiation during development.
The identification of genetic mutations associated with neurodevelopmental disorders (NDDs) along with routine diagnosis based on patients’ characteristics is aiding the delivery of personalized therapies. Dora Tarlungeanu and Gaia Novarino at the Institute of Science and Technology in Klosterneuburg, Austria, review recent advances in genetic technologies, such as whole exome sequencing, that can lead to early intervention, guide choice of treatment and prompt genetic counseling. Introducing the mutations associated with NDDs into model organisms or stem cells is revealing some of the mechanisms underlying NDDs and enabling the evaluation of novel therapeutic strategies that target core symptoms of the disorders. To accelerate the implementation of individualized treatments for NDD the authors highlight the need to adopt interdisciplinary research approaches and to keep clinical staff updated on the latest findings in NDD genetics.
Most of the DNA in the genome does not consist of genes that code for proteins, and understanding the function of these less examined parts of our genetic material is essential to fully understand human development and disease. Brian Gloss and Marcel Dinger at the Garvan Institute of Medical Research in Sydney, Australia, review the challenges and opportunities in unraveling the clinical significance of all parts of our DNA. Many regions of DNA that do not encode protein molecules perform crucial functions in regulating the activity and interactions of the protein-coding genes. Variations in these regions may significantly influence the risks and causes of disease. Studying all parts of the genome will be critical for ensuring that the powerful modern techniques of genetic analysis have maximal impact on healthcare.
Advances in sequencing technologies enable detailed analyses of large genomic alterations, known as structural variations (SV), in human cancer cells. Young Seok Ju and Kijong Yi at the Korea Advanced Institute of Science and Technology in Daejeon, review current knowledge on SV patterns in human cancer genomes and the molecular processes through which they arise. In addition to the loss, gain and reshuffling of large nuclear genetic sequences, cancer cells can also acquire external DNA sequences from viruses, mitochondria, or bacteria that alter gene expression levels or affect gene function. Understanding how these SV drive cancer initiation and progression will not only shed light on the organization and function of the genome, but also provide new opportunities for drug discovery and patient screening that will facilitate a more personalized treatment approach.
Improvements to mouse models for cancer immunotherapy could enhance the precision of new drugs. Immunotherapy trials require genetically modified animal models, including ‘humanized’ mice with a functioning human immune system, and patient-derived xenograft (PDX) mice, in which cells from patients’ tumors are implanted into immunodeficient mice. Charles Lee at the Jackson Laboratory for Genomic Medicine in Farmington, USA, Yeun-Jun Chung at the Catholic University of Korea in Seoul, and co-workers reviewed developments in both PDX and humanized-PDX mouse models for immunotherapy trials. PDX models improve the chances of finding novel biomarkers for drug development. However, humanized PDX mouse models will allow researchers to study diverse cancers in tumour and immune environments as close as possible to those of humans.