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▎ WuXi AppTec content team editor A few days ago, a scientific research team from the Wellcome Sanger Institute in the UK published a paper in the top academic journal Nature, announcing that it has made important progress in sequencing technology.
Scientists have developed a new method called nanorate sequencing (NanoSeq), which is the first to study gene mutations in any human tissue with unprecedented accuracy.
The analysis results using the new technology challenge the traditional view that "cell division is the main mechanism driving mutations.
"
The news of the research institution pointed out that "the new sequencing method represents a huge progress in research in the fields of cancer and aging.
"
A major feature of NanoSeq is that it can detect newly occurring mutations in non-dividing cells.
Human tissue is composed of dividing cells and non-dividing cells.
For example, stem cells continue to divide to maintain self-renewal, and provide cells that no longer divide to maintain the body's operation.
But most cells do not divide or divide very little, such as a large number of newly formed granulocytes in the blood, or neurons in the brain that are almost with us for life.
As we age, genetic changes continue to occur in cells, and it is estimated that 15-40 mutations per year are obtained on average.
Most of the mutations are harmless, but there are also some mutations that can cause cells to become cancerous.
"Somatic mutations drive the development of cancer, and may lead to aging and other diseases.
" The researchers pointed out in the paper, "Although very important, it is very difficult to detect mutations that only exist in a single cell or a few cells.
Image source: 123RF In this study, the research team spent several years improving the duplex sequence method that came out in 2012, including using more specific enzymes to cut DNA more accurately, and improving the biology of sequencing data.
The informatics analysis method ultimately reduced the error rate to less than 5 errors per 1 billion pairs of bases.
Dr.
Robert Osborne, who was responsible for developing this method, pointed out that the improved accuracy of single-cell sequencing allowed scientists to achieve the first Research on DNA changes in human tissues.
Image source: 123RF research team used NanoSeq to detect a variety of tissue samples including blood, brain, muscle, colon, etc.
, and compared the mutation rate and mutation pattern in stem cells and non-dividing cells.
The results of the analysis yielded unexpected findings: the analysis of a large number of blood cells showed that hematopoietic stem cells with a slower division rate and pluripotent progenitor cells with a higher division frequency have a similar number of mutations; neurons that do not undergo cell division have very few divisions.
Muscle cells accumulate mutations at a constant rate, and the rate is similar to that of mitotically active tissues.
These results mean that the relationship between cell division and somatic mutation is different from the previous understanding.
"It is generally believed that cell division is caused by somatic mutation.
The main factor, the more the number of divisions, the more mutations will be produced.
But our analysis found that blood cells that divide many times more than other cells have the same mutation rate and mutation pattern as other cells.
This has changed our understanding of the occurrence of mutations, suggesting that besides cell division, there are other key biological mechanisms that drive mutations.
Dr.
Federico Abascal, the first author of the paper, said.
Image source: 123RF In addition to more accurately detecting mutations in a single DNA molecule, another advantage of the NanoSeq method worth mentioning is that it can collect samples relatively easily, using skin scraping and throat swabs.
Cells are collected for testing in sub-types and other methods, so it is easier to achieve larger-scale research. The researchers pointed out that the new method can observe mutations in various cells, and it will also make large-scale studies of somatic mutations easier, simpler, and more economical.
It will no longer be limited to a few biopsies of a small number of patients, so they believe in NanoSeq.
It will open up new ways to study cancer and aging.
References: [1] Federico Abascal, Luke MR Harvey and Emily Mitchell et al.
(2021).
Somatic mutation landscapes at single-molecule resolution.
Nature.
DOI: 10.
1038/s41586-021-03477-4.
[2] Major advance enables study of genetic mutations in any tissue.
Retrieved May 10, 2021 from
Scientists have developed a new method called nanorate sequencing (NanoSeq), which is the first to study gene mutations in any human tissue with unprecedented accuracy.
The analysis results using the new technology challenge the traditional view that "cell division is the main mechanism driving mutations.
"
The news of the research institution pointed out that "the new sequencing method represents a huge progress in research in the fields of cancer and aging.
"
A major feature of NanoSeq is that it can detect newly occurring mutations in non-dividing cells.
Human tissue is composed of dividing cells and non-dividing cells.
For example, stem cells continue to divide to maintain self-renewal, and provide cells that no longer divide to maintain the body's operation.
But most cells do not divide or divide very little, such as a large number of newly formed granulocytes in the blood, or neurons in the brain that are almost with us for life.
As we age, genetic changes continue to occur in cells, and it is estimated that 15-40 mutations per year are obtained on average.
Most of the mutations are harmless, but there are also some mutations that can cause cells to become cancerous.
"Somatic mutations drive the development of cancer, and may lead to aging and other diseases.
" The researchers pointed out in the paper, "Although very important, it is very difficult to detect mutations that only exist in a single cell or a few cells.
Image source: 123RF In this study, the research team spent several years improving the duplex sequence method that came out in 2012, including using more specific enzymes to cut DNA more accurately, and improving the biology of sequencing data.
The informatics analysis method ultimately reduced the error rate to less than 5 errors per 1 billion pairs of bases.
Dr.
Robert Osborne, who was responsible for developing this method, pointed out that the improved accuracy of single-cell sequencing allowed scientists to achieve the first Research on DNA changes in human tissues.
Image source: 123RF research team used NanoSeq to detect a variety of tissue samples including blood, brain, muscle, colon, etc.
, and compared the mutation rate and mutation pattern in stem cells and non-dividing cells.
The results of the analysis yielded unexpected findings: the analysis of a large number of blood cells showed that hematopoietic stem cells with a slower division rate and pluripotent progenitor cells with a higher division frequency have a similar number of mutations; neurons that do not undergo cell division have very few divisions.
Muscle cells accumulate mutations at a constant rate, and the rate is similar to that of mitotically active tissues.
These results mean that the relationship between cell division and somatic mutation is different from the previous understanding.
"It is generally believed that cell division is caused by somatic mutation.
The main factor, the more the number of divisions, the more mutations will be produced.
But our analysis found that blood cells that divide many times more than other cells have the same mutation rate and mutation pattern as other cells.
This has changed our understanding of the occurrence of mutations, suggesting that besides cell division, there are other key biological mechanisms that drive mutations.
Dr.
Federico Abascal, the first author of the paper, said.
Image source: 123RF In addition to more accurately detecting mutations in a single DNA molecule, another advantage of the NanoSeq method worth mentioning is that it can collect samples relatively easily, using skin scraping and throat swabs.
Cells are collected for testing in sub-types and other methods, so it is easier to achieve larger-scale research. The researchers pointed out that the new method can observe mutations in various cells, and it will also make large-scale studies of somatic mutations easier, simpler, and more economical.
It will no longer be limited to a few biopsies of a small number of patients, so they believe in NanoSeq.
It will open up new ways to study cancer and aging.
References: [1] Federico Abascal, Luke MR Harvey and Emily Mitchell et al.
(2021).
Somatic mutation landscapes at single-molecule resolution.
Nature.
DOI: 10.
1038/s41586-021-03477-4.
[2] Major advance enables study of genetic mutations in any tissue.
Retrieved May 10, 2021 from
