Unlocking the Treasure Trove of Rare CRISPR Systems

A New Search Algorithm Discovers 188 Rare CRISPR Systems in Bacterial Genomes
The researchers at the McGovern Institute for Brain Research at MIT, the Broad Institute of MIT and Harvard, and the National Center for Biotechnology Information (NCBI) at the National Institutes of Health have developed a new search algorithm that has identified 188 kinds of new rare CRISPR systems in bacterial genomes.

The algorithm, which was developed in the lab of pioneering CRISPR researcher Professor Feng Zhang, uses big-data clustering approaches to rapidly search massive amounts of genomic data. The team used their algorithm, called Fast Locality-Sensitive Hashing-based clustering (FLSHclust) to mine three major public databases that contain data from a wide range of unusual bacteria.

The new systems could potentially be harnessed to edit mammalian cells with fewer off-target effects than current Cas9 systems. They could also one day be used as diagnostics or serve as molecular records of activity inside cells.

CRISPR, which stands for clustered regularly interspaced short palindromic repeats, is a bacterial defense system that has been engineered into many tools for genome editing and diagnostics.

The new algorithm allows scientists to parse through data in a time frame that’s short enough to recover results and make biological hypotheses. This allowed researchers to probe billions of protein and DNA sequences in weeks, whereas previous methods that look for identical objects would have taken months.

The researchers found that the thousands of CRISPR systems they discovered fell into a few existing and many new categories. They studied several of the new systems in greater detail in the lab. They also uncovered new mechanisms of action for some Type IV CRISPR systems, and a Type VII system that precisely targets RNA, which could potentially be used in RNA editing.

The scientists say their algorithm could aid in the search for other biochemical systems. The researchers add that their findings illustrate not only how diverse CRISPR systems are, but also that most are rare and only found in unusual bacteria.

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