Barcode from snips
Each person carries in his genotype about 10 million variations, called single nucleotide polymorphisms, or snips (single nucleotide polymorphism, SNP), which represent the difference in just one nitrogen base in the genetic code. Each snip of a person is unique and relatively stable, since it is inherited from parents and extremely rarely mutates. These properties make the SNIP a kind of "barcode" - a distinctive feature that allows you to distinguish the cells of one person from another.
A group of researchers from the Institute of Bioengineering at Harvard University and Harvard School of Medicine has developed a new method of genetic analysis using snips to track changes in the cells of different patients participating in the experiment. This method is faster, simpler and cheaper than existing ones, it allows simultaneous analysis of large groups of cells.
The scope of possible application of the "barcode" system is extensive. For example, when evaluating the effectiveness of an experimental cancer drug that is being tested on different cell lines of different people, it will be possible to determine how the cells of a particular patient respond to treatment and, using this information, develop personalized therapy methods.
Currently, more and more studies are being conducted on the cells of several people at once, they allow us to identify differences in the response to experimental exposure and assess the effect of the genotype on it.
But tracking each cell requires adding special tags and labels to the genome – a cumbersome and expensive process that takes a lot of time. Using snips as barcodes does not affect the quality of the analysis, but it is easier and faster.
Snips are scattered throughout the genome: one snip accounts for about a thousand base pairs. Single snips can be used to distinguish only two people. Commonly used sequencing techniques have a throughput of less than a thousand base pairs. This makes it impossible to determine whether a particular snip belongs to a larger sample.
To overcome this problem, the researchers focused on collecting data from past studies in which whole genomes (and, consequently, snips) of cell lines were sequenced.
Using this data, they created a new method that combines the extraction of genomic DNA from a mixed pool of cells, sequencing of the whole genome of extracted DNA and a computational algorithm that predicts the proportion of each individual cell line in the pool based on known snip profiles.
Determination of cell membership by snips can be used in any number of different experiments in which the effect of several influences is compared (experimental and control groups). The algorithm calculates the fractions of each cell line before and after the experiment and compares them to assess the effect produced by the intervention being tested. The difference in the proportions of cells in the experimental and control groups provides information about the effects exerted during the experiment, as well as whether the cells of a particular organism can have a genetic advantage.
The group tested their method by modeling a pool of cells and changing the number of samples, the number of analyzed snips and the number of changes in the pool. The algorithm produced proportions that corresponded to the simulated ones. He identified up to 500,000 snips in a pool containing cells of up to 1,000 different people.
The researchers also tested their method on B-lymphocytes of people whose genomes were sequenced: it accurately determined the proportions of cells from 50 different cell lines.
The algorithm allows you to simultaneously receive a large amount of information. This will allow researchers to save time and reduce financial costs. In addition, it opens up a new approach in personalized medicine.
The new technology is based on what distinguishes us from each other – unique DNA variations, using them as a tool that will help accelerate scientific breakthroughs.
Article by Y. Chan et al. Enabling multiplexed testing of pooled donor cells through whole-genome sequencing is published in the journal Genome Medicine.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the Wyss Institute: Natural barcodes enable better cell tracking.