Omics Technologies - Genomics


Genomics is the branch of molecular biology concerned with the structure, function, evolution, and mapping of genomes. With respect to personalized medicine the most relevant part is the analysis of genomic sequences for aberrations (mutations, deletions or insertions of pieces of DNA or even translocation of parts of chromosomes). 


What is the major result used in personalized medicine?


Aberrations in the genomic sequence that are known to be associated with hereditary diseases or predisposition for diseases can be detected early on. They can be used to choose a preventive lifestyle (e.g. in case of hereditary obesity or allergies). In case of dangerous mutations that cause trouble later in life tight monitoring of the situation can be initiated (e.g. the BRCA mutations that cause breast cancer after a certain age was reached). In case of cancer tumor genomics can elucidate the driving force of the tumor for better selection of the optimal therapy. 


There are two approaches most commonly used: the whole exome sequencing (WES), which looks only at the part of the genome that encodes for proteins. Considered most important and easiest to interpret, this covers only about 2% of the genome. Thus it is necessarily missing a lot, which will be covered by whole genome sequencing (WGS), which goes after all 3 billion bp of the genome. However, it is much more difficult to interpret this amount of data.


Which body samples are required to carry out the experimental analysis?


General diagnostics of genomic mutations can be done on blood samples as early as a few hours after birth. In case of tumors either circulating tumor cells can be found in the blood or a tumor sample (biopsy) is required. 


Which basic technologies are behind this -omics?


For a long time determining the sequence of genomic DNA was a daunting task causing enormous costs. Today, Next Generation Sequencing (NGS) can deliver a whole human genome in a few days at a cost of US $ 3,000 - 6,000. However, the bioinformatics required to analyze the sequences for informative variations and aberrations is still a difficult task. iEspecially if it aims at new results beyond the easy predefined target regions. 


Fig. 14: Omits schematic overview, major results of genome sequence analysis 


What are the most likely next advances and how would they improve application for personalized medicine?


We all harbor millions of DNA sequence changes as compared to other humans. It is very difficult to determine whether a particular change will cause a disease in the future or not. On top of that many potentially disease-causing variants will do so only in a particular genetic background. Therefore, the connection between several changes needs to be known. The only way to learn about such constellations is to observe and compare the changes in millions of people most of whom will be healthy. These people will help to define the insignificant background of harmless mutations. Further advances in NGS methodologies are already under way, which will allow sequencing genomes of larger and larger groups in an economic way. Technological advance will enable us to gather the enormous amount of data required to reveal many more variation-disease relations that we know today. 


However, this will only become a reality if we all are willing to share our genomic sequences with researchers and medical doctors, i.e. we give our consent to such use. In the end we will all benefit from such consent. 


What’s coming up next?


Next week the topic will be Epigenomics, a rather new field about gene regulation that is strongly influenced by our environment, present and past.