linkstream2 microblog

Lanosterol reverses protein aggregation in cataracts
http://www.nature.com/nature/journal/v523/n7562/full/nature14650.html A finding from rare-disease #exome sequencing cc @solvemendelian

QT:{{”
…Lanosterol is an
amphipathic molecule enriched in the lens. It is synthesized by lanosterol synthase (LSS) in a key cyclization reaction of a cholesterol synthesis pathway. Here we identify two distinct homozygousLSS missense mutations (W581R and G588S) in two families with extensive congenital cataracts. Both of these mutations affect highly conserved amino acid residues and impair key catalytic functions of LSS. Engineered expression of wild-type, but not mutant, LSSprevents intracellular protein aggregation of various
cataract-causing mutant crystallins.
“}}

Multiple hypothesis testing in genomics
http://onlinelibrary.wiley.com/doi/10.1002/sim.6082/full Nice overview, comparing familywise error & FDR control + FDP estimation

http://www.few.vu.nl/~mavdwiel/HDDA/tutorial_multtest.pdf

QT:{{”
This paper presents an overview of the current state-of-the-art in multiple testing in genomics data from a user’s perspective. We describe methods for familywise error control, false discovery rate control and false discovery proportion estimation and confidence, both conceptually and practically, and explain when to use which type of error rate. We elaborate the assumptions underlying the methods, and discuss pitfalls in the interpretation of results. In our discussion we take into account the exploratory nature of genomics experiments, looking at selection of genes before or after testing, and at the role of validation experiments.
“}}

[Protein] Glypican-1 [uniquely] identifies [circulating] cancer #exosomes & detects…cancer
http://www.nature.com/nature/journal/v523/n7559/full/nature14581.html Maybe also for @exRNA

QT:{{”
Exosomes are lipid-bilayer-enclosed extracellular vesicles that contain proteins and nucleic acids. They are secreted by all cells and circulate in the blood. Specific detection and isolation of
…we identify a cell surface
proteoglycan, glypican-1 (GPC1), specifically enriched on
cancer-cell-derived exosomes. GPC1+ circulating exosomes (crExos) were monitored …”}}

http://www.nature.com/nature/journal/v523/n7559/full/nature14581.html

Natural variant of the…#prion protein [G127V] completely
prevents…disease
http://www.nature.com/nature/journal/v522/n7557/full/nature14510.html Under pos. selection for kuru afflicted

QT:{{”
A novel PrP variant, G127V, was under positive evolutionary selection during the epidemic of kuru—an acquired prion disease epidemic of the Fore population in Papua New Guinea—and appeared to provide strong protection against disease in the heterozygous state2. Here we have investigated the protective role of this variant and its interaction with the common, worldwide M129V PrP polymorphism. V127 was seen exclusively on a M129 PRNP allele. We demonstrate that transgenic mice expressing both variant and wild-type human PrP are completely resistant to both kuru…”
“}}

Widespread [25% genes] seasonal…expression reveals [circ]annual differences in…immunity, relevant for vaccination http://www.nature.com/ncomms/2015/150512/ncomms8000/full/ncomms8000.html

In addition to circadian rhythms, batch effects, now consider seasonal effects on gene expression

DNA sequence…#compression
http://bib.oxfordjournals.org/content/16/1/1.full Nice review comparing approaches on 2 axes: classic v Nextgen & reference-based v -free

Not much on LD-based approaches

Zexuan Zhu
Yongpeng Zhang
Zhen Ji
Shan He
Xiao Yang

Brief Bioinform (2015) 16 (1): 1-15.doi: 10.1093/bib/bbt087
First published online: December 3, 2013

Cell Lineage Analysis in Human Brain Using Endogenous Retroelements http://www.sciencedirect.com/science/article/pii/S0896627314011374 Somatic events from #neuron #singlecell WGS

Reconstructing the DNA Methylation Maps of the Neandertal and the Denisovan

David Gokhman,
Eitan Lavi,
Kay Prüfer,
Mario F. Fraga,
José A. Riancho,
Janet Kelso,
Svante Pääbo,
Eran Meshorer,
and Liran Carmel

Science 2 May 2014: 523-527.Published online 17 April 2014

http://www.sciencemag.org/content/344/6181/245.summary

QT:{{”
While enriched with ENCODE biochemical annotations, much of the short-lived constrained sequences we identify are not detected by models optimized for wider pan-mammalian conservation. Constrained DNase 1 hypersensitivity sites, promoters and untranslated regions have been more evolutionarily stable than long noncoding RNA loci which have turned over especially rapidly. By contrast, protein coding sequence has been highly stable, with an estimated half-life of over a billion years (d1/2 = 2.1–5.0). From extrapolations we estimate that 8.2% (7.1–9.2%) of the human genome is presently subject to negative selection and thus is likely to be functional, while only 2.2% has maintained constraint in both human and mouse since these species diverged.
“}}

http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1004525

– pseudoenzyme

http://www.nature.com/nrm/journal/v13/n8/abs/nrm3392.html