Characterization of the… #transcriptome by hybrid sequencing, using Illumina reads to error-correct #PacBio ones
http://www.pnas.org/content/110/50/E4821.long
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The atlas is used to compare regulatory programs between different cells at unprecedented depth, to identify disease-associated regulatory single nucleotide polymorphisms, and to classify
cell-type-specific and ubiquitous enhancers.
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A promoter-level mammalian expression atlas
http://www.nature.com/nature/journal/v507/n7493/full/nature13182.html
An atlas of active enhancers across human cell types and tissues http://www.nature.com/nature/journal/v507/n7493/full/nature12787.html
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:
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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.
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Quite relevant to #transcriptome changes over #development: Earliest Transcribed… Genes Are Short, Newly Evolved…
http://www.cell.com/cell-reports/fulltext/S2211-1247(13)00788-2
Nature. 2013 Aug 29;500(7464):593-7. doi: 10.1038/nature12364. Epub 2013 Jul 28.
Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing.
Xue Z, Huang K, Cai C, Cai L, Jiang CY, Feng Y, Liu Z, Zeng Q, Cheng L, Sun YE, Liu JY, Horvath S, Fan G.
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…We report here a comprehensive analysis of transcriptome dynamics from oocyte to morula in both human and mouse embryos, using single-cell RNA sequencing…. By weighted gene co-expression network analysis, we find that each developmental stage can be delineated concisely by a small number of functional modules of co-expressed genes. This result indicates a sequential order of transcriptional changes in pathways of cell cycle, gene regulation, translation and metabolism, acting in a step-wise fashion from cleavage to morula. Cross-species comparisons with mouse pre-implantation embryos reveal that the majority of human stage-specific modules (7 out of 9) are notably preserved, but developmental specificity and timing differ between human and mouse. Furthermore, we identify conserved key members (or hub genes) of the human and mouse networks.
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Direct Competition between hnRNP C and U2AF65 Protects the
Transcriptome from the Exonization of Alu Elements.
Kathi Zarnack, Julian König, Mojca Tajnik, Iñigo Martincorena, Sebastian Eustermann, Isabelle Stévant, Alejandro Reyes, Simon Anders, Nicholas M Luscombe, and Jernej Ule
There are ∼650,000 Alu elements in transcribed regions of the human genome. These elements contain cryptic splice sites, so they are in constant danger of aberrant incorporation into mature transcripts. Despite posing a major threat to transcriptome integrity, little is known about the molecular mechanisms preventing their inclusion. Here, we present a mechanism for protecting the human transcriptome from the aberrant exonization of transposable elements. Quantitative iCLIP data show that the RNA-binding protein hnRNP C competes with the splicing factor U2AF65 at many genuine and cryptic splice sites. Loss of hnRNP C leads to formation of previously suppressed Alu exons, which severely disrupt transcript function. Minigene experiments explain disease-associated mutations in Alu elements that hamper hnRNP C binding. Thus, by preventing U2AF65 binding to Alu elements, hnRNP C plays a critical role as a genome-wide sentinel protecting the transcriptome. The findings have important implications for human evolution and disease.
Cell, 2013 vol. 152 (3) pp. 453-466
http://www.sciencedirect.com/science/article/pii/S0092867412015450
http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=23374342&retmode=ref&cmd=prlinks
http://www.cell.com/developmental-cell/abstract/S1534-5807%2812%2900142-6
Michal Levin, Tamar Hashimshony, Florian Wagner, and Itai Yanai.
Developmental milestones punctuate gene expression in the
Caenorhabditis embryo. Developmental Cell (May 2012)
Nice disussion of the phylotypic stage .
Figure 4S-E have stage mapping between dmel and celegans
http://www.cell.com/developmental-cell/retrieve/pii/S1534580711001213
Expression time course comparison of orthologs, which are closer than random. Uses sigmoid approximations for gene expression levels — on & off. Discussion on purifying selection related to expression.
Some interesting terms :
http://en.wikipedia.org/wiki/Heterochrony
http://medical-dictionary.thefreedictionary.com/heterometric