Next Generation Sequencing

No doubt there are some great bioinfomatics challenges in using NGS data. Some of these are summarized in a new Trends in Genetics review by Misha Pop and Steven L. Salzberg.

In the paper Pop and Salzberg are quite pessimistic regarding the use of short read sequences in whole genome assembly. Their pessimism is partially based on the lack of paired-end data from NGS technologies which results in fragmented assemblies.

However, as both 454, Solexa and Solid are currently testing and refining paired-end protocols I think that these challenges are likely to be overcome in the near future. Pop and Salzberg quote several simulation studies of the suitability of short reads for genome assembly but unfortunately there are no simulation studies out using short reads along with paired-end information.

This does not have much to do with next generation sequencing but being a bio-geek I could not resit posting a link to Bio-Rad’s new PCR song.

A new study in PNAS by Sugarbaker et al. describes deep sequencing of tumor cDNA using 454 sequencing technology. In the four examined patients, 15 nonsynonymous mutations were discovered: 7 were point mutations, 3 were deletions, 4 were exclusively expressed as a consequence of imputed epigenetic silencing, and 1 was putatively expressed as a consequence of RNA editing. Interestingly, each patient had a different mutation profile, and no mutated gene was previously implicated in the examined cancer type.

The Wall Street Journal has a piece on the study with some interesting perspecives.

Daniel Macarthur over at Genetic Future has an interesting comment about the first two customers who have signed op to get their genome sequenced by personal genomics company Knome.

Sequencing will be done by our collaborator, BGI and supposedly has a price tag of around 350.000$ per genome.

In Sequence has a post on a new ordered array technology developed by Xiaohua Huang’s group at The University of California, San Diego.

The ordered array approach uses a magnet to direct the assembly of DNA particles into a grid-like pattern on a microfluidic chip and offers a promising alternative for a number of high-throughput sequencing platforms that currently use random arrays of DNA molecules.

Ordered arrays could alleviate the problems faced by random arrays, such as low density and low imaging efficiency, and a demand for complex image analysis to recognize the shape, location, and intensity of signals on the chip. Since imaging is a severe bottleneck in most next generation sequencing technologies improvements in this area could dramatically increase throughput.