linkstream2 microblog

Contains information on analysis pipelines and datasets produced from Broad’s Firehose. Access to the protected pages requires an NCI login.

https://confluence.broadinstitute.org/display/GDAC/Home

Colorectal #Cancer Awareness! What Does & Doesn’t Prevent Disease: Vitamins– (including D), Screening++, Exercise++
http://www.slate.com/articles/health_and_science/medical_examiner/2014/03/exercise_prevents_colorectal_cancer_but_vitamins_do_not_advice_from_an_m.html

PARADIGM-SHIFT predicts… function of mutations in… #cancers using pathway[s]. #Network-based gene prioritization
http://bioinformatics.oxfordjournals.org/content/28/18/i640

Nice piece on #SingleCell Seq w/ implications for #cancer, neurosci, &c. Singled out for #sequencing
http://www.nature.com/nmeth/journal/v11/n1/full/nmeth.2768.html HT @naivelocus

Lots on brain, cancer & prenatal sequencing, viz:

QT:{{”
For example, as part of the Single Cell Analysis Program supported by the US National Institutes of Health Common Fund, Kun Zhang’s team will generate full transcriptomes from 10,000 cells in three areas of the human cortex. They will group the transcripts into cell
types—perhaps redefining those cell types in the process—and map the transcripts back to cortical slices of the brain. Single-cell RNA-seq itself is no longer a barrier. “If you have a good cell, and you want to get a measure of the transcriptome, there is more than one option that can lead you to that goal,” Zhang says. In general, however, extracting the neurons posthumously, minimizing RNA degradation and preserving some of the neuronal spatial information is challenging, and the group is evaluating several approaches, Zhang says.
“}}

QT:{{”

…Recurrent mutations in the potassium channel gene KCNJ5 that result in cell depolarization and Ca(2+) influx cause ∼40% of these tumors. We identified 5 somatic mutations (4 altering Gly403 and 1 altering Ile770) in CACNA1D, encoding a voltage-gated calcium channel, among 43 APAs without mutated KCNJ5…. We also identified de novo germline mutations at identical positions in two children with a previously undescribed syndrome featuring primary aldosteronism and neuromuscular abnormalities….
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http://www.ncbi.nlm.nih.gov/pubmed/23913001

Nat Genet. 2013 Sep;45(9):1050-4. doi: 10.1038/ng.2695. Epub 2013 Aug 4.

Somatic and germline CACNA1D calcium channel mutations in
aldosterone-producing adenomas and primary aldosteronism.

Scholl UI, Goh G, Stölting G, de Oliveira RC, Choi M, Overton JD, Fonseca AL, Korah R, Starker LF, Kunstman JW, Prasad ML, Hartung EA, Mauras N, Benson MR, Brady T, Shapiro JR, Loring E, Nelson-Williams C, Libutti SK, Mane S, Hellman P, Westin G, Åkerström G, Björklund P, Carling T, Fahlke C, Hidalgo P,Lifton RP.

http://michorlab.dfci.harvard.edu/publications/Evolutionary%20Theory%20of%20Cancer,%20NYAS2009.pdf

http://www.cancer.gov/cancertopics/understandingcancer/cancergenomics/AllPages

Getting close and personal: Nice pop overview of #cancer genomics & finding new cancer drugs http://econ.trib.al/DevSlDS HT @ElementoLab

http://www.economist.com/news/science-and-technology/21592599-researchers-and-drug-companies-are-ganging-up-new-push-against

.@drbachinsky Basically, SNP w. prostate #cancer risk + mechanistic insight …allele at 6q22 increases RFX6 expr…
http://go.nature.com/HEpOHG

http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.2862.html

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.