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DNA Sudoku

Erin Podolak

Combining a Chinese math theorem with elements of cryptology, scientists have developed "DNA Sudoku" to sequence thousands of DNA samples at one time.

A team of researchers at Cold Spring Harbor Laboratory (CSHL) have developed a new way to sequence genetic information that will save scientists time and money. “DNA Sudoku” harnesses the 2,000-year-old Chinese mathematical theorem and the concepts of cryptology that are used in Sudoku puzzles to sequence genomes more efficiently.

Tens of thousands of samples can be combined and sequenced at once in a process known at multiplexing. Previous multiplexing attempts were slow and tedious, because each sample first had to be tagged with a barcode oligonucleotide before it could be mixed with other samples. The tags were the only way scientists could tell which resulting sequences corresponded with which samples. "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," said Yaniv Erlich, first author on the DNA Sudoku paper.

To streamline the multiplexing process, Erlich and other researchers at CSHL mixed the samples in specific patterns, creating sample pools that only had to be tagged once as a group. "Since we know which pool contains which samples, we can link a sequence to an individual sample with high confidence," said Erlich. The pooling strategy is based on the Chinese remainder theorem that lies behind Sudoku. Currently the technology has been the most successful in genetic analyses that only need to sequence small segments of a genome to look for a certain variant of a gene or a mutation. As the technology improves it may find wider clinical applications such as HLA typing.

Traditional sequencing methods work with a single DNA sample at a time. Even when using a multiplexing approach, researchers previously could only work with samples sizes of a few hundred. The CSHL method has blown away these other methods. "In theory, it is possible to use the Sudoku method to sequence more than a hundred thousand DNA samples," said Gregory Hannon, leader of the team that invented the Sudoku approach. "Sequencing many samples at once could take project costs of over $10 million and reduce them to merely $50,000," said Hannon.

The team at CSHL is looking into collaborative research with Dor Yeshorim, an organization that has collected DNA from thousands of Jewish orthodox communities to study genetic diseases like Tay-Sachs and cystic fibrosis, which occur frequently in specific ethnic groups. Using the DNA Sudoku. method researchers should be able to quickly identify individuals in the sample population carrying mutations for genetic disease.

CSHL is a private research institution working on molecular biology and genetics. The research team has patented the DNA Sudoku method. Their report will be published in the journal Genome Research.