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Concept
Sequence assembly
Summary
In bioinformatics, sequence assembly refers to aligning and merging fragments from a longer DNA sequence in order to reconstruct the original sequence. This is needed as DNA sequencing technology might not be able to 'read' whole genomes in one go, but rather reads small pieces of between 20 and 30,000 bases, depending on the technology used. Typically, the short fragments (reads) result from shotgun sequencing genomic DNA, or gene transcript (ESTs).
The problem of sequence assembly can be compared to taking many copies of a book, passing each of them through a shredder with a different cutter, and piecing the text of the book back together just by looking at the shredded pieces. Besides the obvious difficulty of this task, there are some extra practical issues: the original may have many repeated paragraphs, and some shreds may be modified during shredding to have typos. Excerpts from another book may also be added in, and some shreds may be completely unrecognizable.
The first sequence assemblers began to appear in the late 1980s and early 1990s as variants of simpler sequence alignment programs to piece together vast quantities of fragments generated by automated sequencing instruments called DNA sequencers. As the sequenced organisms grew in size and complexity (from small viruses over plasmids to bacteria and finally eukaryotes), the assembly programs used in these genome projects needed increasingly sophisticated strategies to handle:
terabytes of sequencing data which need processing on computing clusters;
identical and nearly identical sequences (known as repeats) which can, in the worst case, increase the time and space complexity of algorithms quadratically;
DNA read errors in the fragments from the sequencing instruments, which can confound assembly.
Faced with the challenge of assembling the first larger eukaryotic genomes—the fruit fly Drosophila melanogaster in 2000 and the human genome just a year later,—scientists developed assemblers like Celera Assembler and Arachne able to handle genomes of 130 million (e.
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