linkstream2 microblog

https://www.cell.com/cell/fulltext/S0092-8674(18)31633-7

Characterization of #SVs w. single molecule & hybrid sequencing http://bioinformatics.oxfordjournals.org/content/30/24/3458.abstract Probabilistic read mapping, re-evaluating adjacencies

QT:{{"
We present MultiBreak-SV, an algorithm to detect structural variants
(SVs) from single molecule sequencing data, paired read sequencing
data, or a combination of sequencing data from different platforms.
"}}

https://bitbucket.org/remills/svelter

predict bkpts & assess

QT:{{”
We introduce GASVPro, an algorithm combining both paired read and read depth signals into a probabilistic model that can analyze multiple alignments of reads.
“}}

http://genomebiology.com/2012/13/3/R22

QT:{{”
We present MultiBreak-SV, an algorithm to detect structural variants (SVs) from single molecule sequencing data, paired read sequencing data, or a combination of sequencing data from different platforms. “}}

uses pacbio

http://bioinformatics.oxfordjournals.org/content/30/24/3458.long

@markgerstein: Korbel mentions: Criteria for Inference of
Chromothripsis in Cancer Genome
http://t.co/TslcrZsmNv #BTGCG14

http://www.sciencedirect.com/science/article/pii/S0092867413002122

Transduction of nonrepetitive DNA mediated by L1 retrotransposition in #cancer #genomes
http://www.sciencemag.org/content/345/6196/1251343.abs associated w/ hypomethylation

Jose M. C. Tubio1,
Yilong Li1,*,
Young Seok Ju1,*,
Inigo Martincorena1,
Susanna L. Cooke1,
…
Adrienne M. Flanagan30,31,
P. Andrew Futreal1,32,
Sam M. Janes3,
G. Steven Bova12,
Michael R. Stratton1,
Ultan McDermott1,
Peter J. Campbell1,10,33,‡

QT:{{”
Retrotransposons are DNA repeat sequences that are constantly on the move. By poaching certain cellular enzymes, they copy and insert themselves at new sites in the genome. Sometimes they carry along adjacent DNA sequences, a process called 3′ transduction. Tubio et al. found that 3′ transduction is a common event in human tumors. Because this process can scatter genes and regulatory sequences across the genome, it may represent yet another mechanism by which tumor cells acquire new mutations that help them survive and grow.
“}}

Hypomethylation in the human germline associates w/ structural mutability: Many #SVs in #genomic #methylation deserts
http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002692

Genomic hypomethylation in the human germline associates with selective structural mutability in the human genome.
http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002692

Li J, Harris RA, Cheung SW, Coarfa C, Jeong M, Goodell MA, White LD, Patel A, Kang SH, Shaw C, Chinault AC, Gambin T, Gambin A, Lupski JR, Milosavljevic A.

PLoS Genet. 2012;8(5):e1002692. doi: 10.1371/journal.pgen.1002692. Epub 2012 May 17.
PMID: 22615578 [PubMed – indexed for MEDLINE] Free PMC Article

Mutability as a measure of methylation, viz:
QT:{{
The MI model is based on the fact that in mammals DNA methylation predominantly occurs in CpG dinucleotides, increasing the probability of transitions to TpG or CpA dinucleotides. The MI calculation by Sigurdsson et al. [48] implicitly uses mutability of CpGs in the human genome as an indicator of methylation in the germline. We apply this method of by integrating four million non-redundant SNPs from the HapMap project. Methylation index values were calculated for the same set of 100 Kbp windows used for sperm methylome construction to facilitate comparison.
}}

Also :

Confounding by repetitive elements and CpG islands does not explain the association between hypomethylation and genomic instability. http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1003333

Harris RA, Shaw C, Li J, Cheung SW, Coarfa C, Jeong M, Goodell MA, White LD, Patel A, Kang SH, Chinault AC, Gambin T, Gambin A, Lupski JR, Milosavljevic A.

PLoS Genet. 2013;9(2):e1003333. doi: 10.1371/journal.pgen.1003333. Epub 2013 Feb 28. No abstract available.
PMID: 23468659 [PubMed – indexed for MEDLINE] Free PMC Article

http://www.nature.com/ncomms/2014/140205/ncomms4216/full/ncomms4216.html Mentioned as a mechanism for “occasional presence of templated insertions.”

Long-span PET mapping reveals characteristic patterns of #SVs in… cancer [v norm] genomes, but no MEIs or small events
http://genome.cshlp.org/content/early/2011/04/05/gr.113555.110.abstract

The described study used long paired-end-tags (PET) to analyze and compare SVs in cancer and normal genomes. It determined the prevalence of different types of SVs in normal and cancer sample. Overall, the results are interesting and convincing on a qualitative level; however, for the reasons outlined below, more precise and quantitative delineation of the observed effects is highly desirable.

1) Small sample size of normal genomes (only 2 normal genomes)

2) Validation rate was low (< 77%) for everything except deletions, and for singletons it was even lower. .

3) Long PET is not good for finding smaller events (few kbps). Thus, this analysis missed smaller scale SVs and cancer rearrangements.

4) While there is a discussion about breakpoints and associated repeats, it is not very informative as breakpoint locations were not determined to basepair resolution.

5) No MEI were considered — particularly, no cancer MEI were considered in the analysis, while recently it was found that somatic retrotransposition occurs in cancer (Lee et al., PMID: 22745252)..

Comprehensive long-span paired-end-tag mapping reveals characteristic patterns of structural variations in epithelial cancer genomes –

Hillmer AM, Yao F, Inaki K, Lee WH, Ariyaratne PN, Teo AS, Woo XY, Zhang Z, Zhao H, Ukil L, Chen JP, Zhu F, So JB, Salto-Tellez M, Poh WT, Zawack KF, Nagarajan N, Gao S, Li G, Kumar V, Lim HP, Sia YY, Chan CS, Leong ST, Neo SC, Choi PS, Thoreau H, Tan PB, Shahab A, Ruan X, Bergh J, Hall P, Cacheux-Rataboul V, Wei CL, Yeoh KG, Sung WK, Bourque G, Liu ET, Ruan Y.

Genome Res. 2011 May;21(5):665-75. doi: 10.1101/gr.113555.110. Epub 2011 Apr 5.