http://www.ncbi.nlm.nih.gov/pubmed/23925245
Contains a personal-genome like construction for HeLa
with 100X shotgun and then paired ends used for variant discovery and sequencing of pools of fosmid clones for haplotype resolution. Finally, low-freq. somatic and passage variants layered onto this.
Haplotype-resolved genome… of #HeLa: Has mapping of #ENCODE RNA- & chIP-seq against a personal genome
http://dx.doi.org/10.1038/nature12213 via @aemonten
Genome Biol. 2012 Dec 13;13(12):R115.
Whole-genome reconstruction and mutational signatures in gastric cancer. Nagarajan N, Bertrand D, Hillmer AM, Zang ZJ, Yao F, Jacques PE, Teo AS, Cutcutache I, Zhang Z, Lee WH, Sia YY, Gao S, Ariyaratne PN, Ho A, Woo XY, Veeravali L, Ong CK, Deng N, Desai KV, Khor CC, Hibberd ML, Shahab A, Rao J, Wu M, Teh M, Zhu F, Chin SY, Pang B, So JB, Bourque G, Soong R, Sung WK, Tean Teh B, Rozen S, Ruan X, Yeoh KG, Tan PB, Ruan Y.
http://www.ncbi.nlm.nih.gov/pubmed/23237666
Some thoughts, much from WC:
Looks like the data is freely available via GEO ID : GSE30833 http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE30833
The article by Nagarajan et al. highlights the authors efforts to utilize de novo genome assembly of gastric cancer genomes to detect not only single nucleotide variants (SNV’s) and short
insertions/deletions (indels), but also larger scale genomic structural variation (SV) that could be signatures of cancer genomes. It is to be applauded that this is a whole genome analysis.
The authors present several interesting findings such as enrichment for C->A and T->A mutations in both cancer genomes, enrichment for C->A and C->T mutations in the H. pylori infected cancer genome (evidence of cytosine specific transcription mediated DNA repair due to deamination), and amplification and deletion of regions on chromosome 12 in the non-H. pylori infected genome.
Although copy number variants (CNV) could potentially be detected by exome sequencing alone, whole genome sequence enables the precise localization of such events, as well as the detection of variation in non-coding regions.
Their methodology relies on combining high-throughput short-read sequencing with longer DNA-PET (paired end tags) in order to construct higher confidence de novo assemblies with longer contiguous regions.
QT:”One implication of this realization is that recent mutation may have a greater influence on disease susceptibility or protection than is conferred by variations that arose in distant ancestors.” http://www.ncbi.nlm.nih.gov/pubmed/21962505
http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.2768.html Replicative mechanisms for #CNV formation are error prone: CNVs associated with SNVs in 67 cases http://dx.doi.org/10.1038/ng.2768 MT @LeucineRichBio
Lupski paper
http://www.nature.com/nmeth/journal/vaop/ncurrent/full/nmeth.2651.html
Network-based stratification of tumor mutations
Matan Hofree,
John P Shen,
Hannah Carter,
Andrew Gross
& Trey Ideker
Nature Methods(2013)doi:10.1038/nmeth.2651
QT:”
Our results suggest that the evolutionary properties of copy-number mutation differ significantly from other forms of genetic mutation and, in contrast to the hominid slowdown of single-base-pair mutations, there has been a genomic burst of duplication activity at this period during human evolution.
”
http://www.nature.com/nature/journal/v457/n7231/full/nature07744.html
This is a paper on increased rates of segmental duplications along the lineage to human and chimp.
This should have some implications for pseudogene numbers between organisms.
QT:”
We estimate that approximately 73% of all protein-coding SNVs and approximately 86% of SNVs predicted to be deleterious arose in the past 5,000–10,000 years.
”
6,515 #exomes reveals the recent origin of most human protein-coding variants: ~75% #SNVs arose in last ~7.5K yrs
http://www.nature.com/nature/journal/v493/n7431/full/nature11690.html
The bread #wheat genome using… shotgun sequencing: ~5X human, from 3 diff. component genomes, many #pseudogenes
http://www.nature.com/nature/journal/v491/n7426/full/nature11650.html
http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1003709#pgen-1003709-g006
This paper discusses gene intolerance score — very similar to depletion of common polymorphisms. They don’t analyze non-coding regions — this is using exome data only. Blue for tolerant and red for intolerant (see Figure 1) .
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