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Scientists thing the new method can save millions in sequencing costs

Scientists at the Cold Spring Harbor Laboratory (CSHL) have discovered a new method of pooling a multitude of DNA samples for sequencing. The new method is being called DNA Sudoku because it uses a method similar to the math game to greatly increase the speed at which DNA can be sequenced.

The researchers report that DNA Sudoku method allows for tens of thousands of DNA samples, short combinations of polynucleotides with A, T, G, and C bases, to be combined and sequenced.  The simultaneous sequencing is done by looking at the letter order and comparing it to the correct order of the known human genome using an algorithm that resembles those used to solve Soduku puzzles.

The ability to do all the sequencing at once is a massive improvement over past methods that allowed only a single DNA sample to be sequenced at a time. It is also an improvement on current techniques that can ideally only combine hundreds of samples.

Researcher Gregory Hannon, Ph.D. said, "In theory, it is possible to use the Sudoku method to sequence more than a hundred thousand DNA samples." Hannon is a genomics expert and the leader of the team that invented the Sudoku approach.

The Sudoku method was originally developed to help solve a problem that was plaguing one of the labs research projects and the researchers discovered that the method had promise for clinical applications. According to Hannon, the technique can be used to analyze specific regions of genomes form a large population to identify those who carry genetic mutations that may cause genetic disease.

Another of the key benefits of the Sudoku technique is that it is much cheaper that the current methods used by researchers. A sequencing project using current methods can cast around $10 million according to Hannon and using his team's new approach a project of similar size might possibly be done for $50,000 to $80,000.

In traditional multiplexing -- sequencing high number of DNA samples at one -- each sample had to be first tagged with a barcode. With the Sudoku method the researchers would only need to tag each pool of samples with a barcode.

Researcher Yaniv Erlich said, "It's time-consuming and costly to have to design a unique barcode for each sample prior to sequencing, especially if the number of samples runs in the thousands."

Erlich continued saying, "Since we know which pool contains which samples [with the Sudoku method], we can link a sequence to an individual sample with high confidence."

The Sudoku method is currently ideally used on genotype analyses that need only short segments of an individual's genome. Clinical applications for the new method could be for HLA typing, which is a diagnostic tool for predicting the risk of organ transplant, cancer, and autoimmune disease.




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