How does multiple-testing correction work
http://www.nature.com/nbt/journal/v27/n12/abs/nbt1209-1135.html Intuition for teaching: genome-wide error rate on a single gene v family
Archive for the 'SciLit' Category
How does multiple testing correction work?
June 13, 2016The role of regulatory variation in complex traits and disease : Nature Reviews Genetics : Nature Publishing Group
June 12, 2016Reg. variation in cplx traits by @LeonidKruglyak
http://www.nature.com/nrg/journal/v16/n4/full/nrg3891.html nice teaching figure for #eQTLs, showing how mostly cis + hotspots http://www.nature.com/nrg/journal/v16/n4/full/nrg3891.html
Landscape of somatic retrotransposition in human cancers. – PubMed – NCBI
May 27, 2016Landscape of somatic retrotransposition in human cancers
http://science.sciencemag.org/content/337/6097/967.long 194 insertions in 43 WGS, mostly L1s w. ~50% near genes
Landscape of Somatic Retrotransposition in Human Cancers
Eunjung Lee1,2,
Rebecca Iskow3,
Lixing Yang1,
Omer Gokcumen3,
Psalm Haseley1,2,
Lovelace J. Luquette III1,
Jens G. Lohr4,5,
Christopher C. Harris6,
Li Ding6,
Richard K. Wilson6,
David A. Wheeler7,
Richard A. Gibbs7,
Raju Kucherlapati2,8,
Charles Lee3,
Peter V. Kharchenko1,9,*,
Peter J. Park1,2,9,*,
The Cancer Genome Atlas Research Network
Science 24 Aug 2012:
Vol. 337, Issue 6097, pp. 967-971
DOI: 10.1126/science.1222077
The paper describes the analysis of transposable elements (TE) insertions at single nucleotide resolution in 43 high coverage whole genome datasets from five cancer types. The authors developed a computational method that uses as input paired-end whole genome sequence data from tumor and normal sample aligned against a reference genome and a custom repeat assembly of TE sequences to detect the position and mechanism of TE insertion. The method identified 194 TE insertions (183 L1s, 10 Alus and 1 ERV). The diversity in the frequency of TE insertions in the same cancer type (ranging from 45-60 to 106 events per tumour) suggests the presence of tumour subtypes with respect to TE activity.
By intersecting the 194 TE with genome annotation, the authors found that 64 TE are in known genes (in UTRs and introns), most of which are implicated in tumour suppressor functions. Also, the TE events targeted genes that are frequently/recurrently mutated, suggesting that TE insertions can potentially contribute to cancer development. Gene expression analysis showed that TE insertion results in significantly decreasing the expression levels for the host gene. TE orientation also has an impact on the expression level, with antisense insertion being less disruptive.
Comparing the germline and somatic insertion sites shows notable differences. Germline L1s are significantly more depleted from genes compared to somatic L1s. Somatic L1s are significantly overrepresented within regions of DNA hypomethylation suggesting the DNA
hypomethylation promoted L1 integration.
Computational Medicine: Translating Models to Clinical Care | Science Translational Medicine
May 22, 2016Principles of scientific research team formation and evolution
May 22, 2016structures for team science
http://www.pnas.org/content/111/11/3984.full
Genome-wide association study identifies 74 loci associated with educational attainment : Nature : Nature Publishing Group
May 21, 2016GWAS identifies 74 loci associated w. educational attainment http://www.nature.com/nature/journal/vaop/ncurrent/full/nature17671.html Described in 3 pgs of main text & 146 pgs of supplement
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature17671.html
From Scientific Discovery to Cures: Bright Stars within a Galaxy: Cell
May 18, 2016http://www.cell.com/cell/abstract/S0092-8674(15)01127-7?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867415011277%3Fshowall%3Dtrue
Lalonde E*, Ishkanian AS*, ….P’ng C, Collins CC, Squire JA, Jurisica I, Cooper C, Eeles R, Pintilie M, Dal Pra A, Davicioni E, Lam WL, Milosevic M, Neal DE, van der Kwast T, Boutros PC, Bristow RG (2014) “Tumour genomic a nd microenvironmental heterogeneity as integrated predictors for prostate cancer recurrence: a retrospective study” La ncet Oncology 15(13):1521-1532 (PMID: 25456371)
May 17, 2016Genomic & microenvironmental heterogeneity as integrated predictors for prostate #cancer recurrence
http://www.ncbi.nlm.nih.gov/pubmed/25456371 CNVs & hypoxia
* Lalonde E*, Ishkanian AS*, ….P’ng C, Collins CC, Squire JA, Jurisica I, Cooper C, Eeles R, Pintilie M, Dal Pra A, Davicioni E, Lam WL, Milosevic M, Neal DE, van der Kwast T, Boutros PC, Bristow RG (2014) “Tumour genomic and microenvironmental heterogeneity as integrated predictors for prostate cancer recurrence: a retrospective study” Lancet Oncology 15(13):1521-1532 (PMID: 25456371)
The novelty of the paper is that it is the first study integrating DNA-based signatures and microenviroment-based signature for cancer prognosis. The authors found four prognostic indices, i.e. cancer genomic subtype (generated from clusters of CNV profiles), genomic instability (represented by the percentage of genome alteration), DNA signature (276 genes identified from random forests), and tumor hypoxia (the microenvironment signature), to be effective in predicting patient survival in different groups. Standard clinical univariate and multivariate analyses were performed.
Timing, rates and spectra of human germline mutation : Nature Genetics : Nature Publishing Group
May 17, 2016Timing, rates & spectra of human germline mutation
http://www.nature.com/ng/journal/v48/n2/full/ng.3469.html Metaanalysis of >6500 events gives a de novo mutational signature
linkstream2 microblog 