Posts Tagged ‘encode’

DNA’s secret weapon against knots and tangles

May 7, 2017

DNA’s secret weapon against knots & tangles Quick overview of recent models of loop extrusion w/ cohesin & CTCF

Shedding light on the dark proteome

April 24, 2017

“The dark proteome could be an evolutionary playground for trying out new folds

Ultimately one would expect particularly useful variations to get fixed at the genetic level. But it needn’t be where that variation begins. What’s more, organisms needn’t be quite so dependent for their molecular repertoire on their evolutionary heritage. O’Donoghue thinks that all organisms probably have a significant fraction of proteins unique just to them.

‘The fact that the dark matter of the proteome has less evolutionary constraint than the other bits of proteome may suggest that it’s under less selection,’ says Gerstein. ‘This is perhaps because it’s more flexible structurally, but also in a sense more flexible in terms of accommodating various amino-acid changes compared to the structurally inflexible and fixed parts of the crystallised proteome.’ This adds momentum to the picture of genomics as a rather more fluid affair than is suggested by the old picture of identical proteins being
mass-produced from a fixed genetic template.

Gerstein feels that studying the dark proteome opens up a host of interesting questions. For example, although known bacteria have a smaller dark proteome than eukaryotes, there’s a huge ‘dark
microbiome’ of unculturable bacteria. Might that be more full of dark proteins – perhaps useful ones?

And what about us? ‘How does the human dark proteome compare to that of eukaryotes as a whole?’ Gerstein wonders. How well, really, do we know ourselves?”

Shedding light on the dark proteome

The International Human Epigenome Consortium: A Blueprint for Scientific Collaboration and Discovery. – PubMed – NCBI

April 16, 2017

#IHEC: A Blueprint for…Collab. & Discovery Summary bullets on heterogeneity, disease, rel. to SNPs, comp. tools

whole genome assembly from Hi-C data

April 2, 2017

De novo assembly of the A aegypti genome using #HiC, by @erezaterez et al Works on human too, w. promise for #SVs

De novo assembly of the Aedes aegypti genome using Hi-C yields chromosome-length scaffolds

Olga Dudchenko1,2,3,4,
Sanjit S. Batra1,2,3,*,
Arina D. Omer1,2,3,*,
Sarah K. Nyquist1,3,
Marie Hoeger1,3,
Neva C. Durand1,2,3,
Muhammad S. Shamim1,2,3,
Ido Machol1,2,3,
Eric S. Lander5,6,7,
Aviva Presser Aiden1,2,8,9,
Erez Lieberman Aiden1,2,3,4,5,†

Science 23 Mar 2017:
DOI: 10.1126/science.aal3327

on whole genome assembly from Hi-C reads. There is also some info on chromosomal rearrangement from Hi-C.

Inferring chromatin-bound protein complexes from genome-wide binding assays – Genome Research

February 26, 2017

Inferring [w. NMF] chromatin-bound protein complexes [of TFs] from [ENCODE ChIP-seq] binding assays, by @ElementoLab

Giannopoulou E, Elemento O. 2013. Inferring chromatin-bound
protein complexes from genome-wide binding assays. Genome Research, Published in Advance April 3, 2013, doi: 10.1101/gr.149419.112.

This study uses nonnegative matrix factorization (NMF) of ENCODE CHIP-seq data (transcription
factors and histone modifications) to predict complexes of
transcription factors that bind DNA
together; it then assesses how these predicted complexes regulate gene expression. It goes beyond
previous studies in that it attempts to treat the TFs as complexes rather than individuals. A handful of
the predicted complexes correspond to known regulatory complexes, e.g. PRC2, and overall, the
complexes were enriched for known protein-protein interactions. Linear regression and random forest
models were then used to predict the effects of the complexes on the expression of adjacent genes. In
both models, the complexes performed better than those predicted from a scrambled TF read count
matrix. Overall, this study provides a large set of hypotheses for combinations of TFs that may
function together, as well as potential new components of known complexes.

The dark side of the human genome : Nature : Nature Research

November 27, 2016

Dark side of the..genome QT: NextGen..has been..the tech engine of #ENCODE..but..hi-res livecell imaging [is coming]

Has figure from Khurana et al. Nat. Rev. Genet. (’16)

“Next-generation sequencing has been — and still is — the
technological engine of ENCODE. But looking ahead, researchers might be able to roll out high-resolution live-cell imaging on a large scale to watch the state of the genome change in real time using specific markers. This technology could be disruptive. “If we had a better microscope, we wouldn’t be sequencing anymore,” says

Species-Specific | The Scientist Magazine(R)

September 6, 2015

Scientists uncover striking differences between mouse and human gene expression across a variety of tissues.
By Jyoti Madhusoodanan | November 17, 2014

The results “go a little against the grain,” said bioinformatician Mark Gerstein of Yale University who was not involved in the study. “We might think that humans and mice are very similar [genetically], but when we compare their transcriptomes, they’re more different than we thought.”

Single-cell chromatin accessibility reveals principles of regulatory variation : Nature : Nature Publishing Group

August 28, 2015

#SingleCell chromatin accessibility >1.6k ATAC-seq expts; many on @ENCODE_NIH cell lines H1, GM12878 & K562

PLOS Genetics: 8.2% of the Human Genome Is Constrained: Variation in Rates of Turnover across Functional Element Classes in the Human Lineage

August 2, 2015

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.

Inferring gene regulatory logic from high-throughput measurements of thousands of systematically designed promoters : Nature Biotechnology : Nature Publishing Group

June 10, 2015

Segal cites: Measurements of 1000s of…designed promoters Num. binding sites correlated w/ expr., for 1st few #ICSG2015