October 23, 2018
On October 18-19 researchers of NLA took part at the Sino-French-Kazakh Workshop on Innovative Therapeutic Solutions for Cancer and Ageing diseases, that was organized by International Bio-Business Services (IBBS) with the support of the French Embassy in Kazakhstan, Nazarbayev University and the Sino-French School of Oncology.
The workshop brought together Kazakh, Chinese and French participants from academic and medical institutions as well as industrial players to share their views and knowledge in order to strengthen international cooperation and establish new interactive programs.
Ainur Akilzhanova, head of Laboratory of Genomic and Personalized Medicine, NLA and Ulykbek Kairov, head of Laboratory of Bioinformatics and Computational Systems Biology, NLA presented their research on clinical interpretation and implications of whole genome/ whole exome sequencing for cancer and aging diseases.
Whole-genome sequencing (WGS) and whole exome sequencing (WES) are increasingly applied in clinical medicine and is expected to uncover clinically significant findings regardless of sequencing indication. The promise of personalized medicine depends on the ability to integrate genetic sequencing information into disease risk assessment for individuals. Genomic sequencing technology is moving rapidly from the research setting into clinical medicine but significant technological and interpretive challenges remain.
Aim of this study was to evaluate the clinical utility of WGS/WES in a group of healthy Kazakh population regarding the detection of genetic variants associated with predisposition to various clinical conditions and drug response.
Researchers presented findings from an exploratory study of 115 participants, most of whom identified themselves as Kazakh (up to at list 3 generations). Participants aged 18-65 years answered questions about the reasons they consented to study and about what they anticipated would come of genomic sequencing, demographic data, risk factors, family history and ancestry questions. None of the study participants had manifest inherited disease. gDNA was extracted from blood. DNA libraries were performed using Nextera DNA Library Preparation Kit (Illumina, USA). For WES gDNA was fragmented, then DNA libraries were performed using SureSelect Human All Exon V5+UTRs kit (Agilent Technologies). Sequencing was performed on Illumina HiSeq2000 platform with min coverage 30x (WGS) and 100x(WES). Bioinformatic analysis was done. Data was compared with data of existing international databases (COSMIC, ESP600, ClinVar, PharmGKB etc) to identify clinical genomic variants in our data. Mendelian variants were compared with ACMG-reportable genes, HGMD. Molecular diagnostics requires accurate and consistent classification of sequence variants (i.e., single nucleotide variants (SNVs) and deletion/insertion (indels) variants). Detection of a pathogenic or “actionable” variant may influence a patient's diagnosis and/or prognosis, family planning, and lifelong health management.
Several genetic variants with clinical implications were identified in all healthy participants. Detected variants are presented grouped into categories in the report delivered to healthy person – predisposition to clinical conditions, inherited disorders (if any), cancer, cardiovascular risks, drug response etc. More promising using targeted NGS for molecular characterization of cancer and aging disease. Compared to broader approaches, such as WGS, targeted sequencing is a more cost-effective method for investigating areas of interest. Targeted resequencing enables researchers to focus on regions that are most likely to be involved in the phenotype under study, conserving resources and generating a smaller, more manageable data set. Targeted approaches can also deliver much higher coverage levels, allowing identification of variants that are rare and more expensive with whole-genome or Sanger sequencing.
WGS/WES seems be the method of choice not only in cases with a specific clinical phenotype in need of reaching a diagnosis but also in the context of carrier screening. The disclosure of the NGS results to the patient is not an issue, if genetic counseling by a healthcare provider with genetic background is provided before and after test according to international guidelines. Targeted approaches using next-generation sequencing (NGS) allow researchers to focus time, expenses, and data analysis on specific areas of interest.
During the Sino-French-Kazakh Workshop were presented also reports on the possible applications of electromagnetic fields for cancer treatment (Dinara Begimbetova, senior researcher, Laboratory of Translational Medicine and Life Sciences Technologies, NLA), reports on robust approach for analysis and interpretation of tumor transcriptomes from high-throughput genomic platforms for investigation of hidden signals (Ulykbek Kairov, Laboratory of Bioinformatics and Computational Systems Biology, NLA) and others.