3D clusters of somatic mutations…reveal numerous rare mutations as functional targets
https://GenomeMedicine.BiomedCentral.com/articles/10.1186/s13073-016-0393-x Introduces 3DHotSpots, which is one of a number of recent approaches (incl. CLUMPS, Hotspot3D, Mutation3D & HotMAPS) for finding groupings of somatic SNVs via structure
Archive for the 'SciLit' Category
JClub by BW on “3D clusters of somatic mutations in cancer reveal numerous rare mutations as functional targets”, Genome Medicine
February 4, 2018A Bayesian Framework to Account for Complex Non-Genetic Factors in Gene Expression Levels Greatly Increases Power in eQTL Studies
January 6, 2018A Bayesian Framework to Account for Complex Non-Genetic Factors in Gene Expression Levels Greatly Increases Power in #eQTL Studies http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1000770 Early discussion & development of PEER factors
Cutting Edge: Building bridges between cellular and molecular structural biology
December 22, 2017Cutting Edge: Building bridges between cellular & mol. structural biology https://ELIFEsciences.org/articles/25835 quote: “The use of structured biological #annotation is not common practice in
#cryoEM…[but] by the end of the meeting there was a clearer appreciation of the importance of [this]”
QT:{{”
As previously explained, structured biological annotation is the association of data with identifiers and ontologies taken from well-established bioinformatics resources. The use of structured biological annotation is not common practice in the electron microscopy or structural biology communities. Therefore, ontology experts were invited to the workshop to explain why these are useful and what resources and tools are available for assigning annotations. Use-cases such as mouse imaging data helped to explain the principles and practice of structured biological annotation. By the end of the meeting there was a clearer appreciation of the importance of structured biological annotation for searching and linking imaging data across different scales, between different imaging and structural databases and with other bioinformatics resources.”
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Cryo-EM Structures of the Magnesium Channel CorA Reveal Symmetry Break upon Gating – ScienceDirect
November 30, 2017QT:{{”
• Find 3.8 Å resolution cryo-EM structure of the ∼200 kDa magnesium channel CorA • Mg2+-free CorA exhibits dramatic loss of symmetry in the cytoplasmic domain …
• Inter-subunit Mg2+ is important for stabilizing the closed state of CorA “}}
#CryoEM Structures of the Mg++ Channel CorA Reveal Symmetry Break upon Gating https://www.ScienceDirect.com/science/article/pii/S0092867415017195 In closed conformation: 5 identical subunits arranged tightly around 5-fold axis & pore. In open: they lose bridging ions & open to differing degrees with helix-hinging motions.
Matthies D1, Dalmas O2, Borgnia MJ1, Dominik PK2, Merk A1, Rao P1, Reddy BG2, Islam S2, Bartesaghi A1, Perozo E3, Subramaniam S4. Cell. 2016 Feb 11;164(4):747-56. doi: 10.1016/j.cell.2015.12.055.
differential privacy
November 29, 2017”
Box 1 of the following paper has a nice definition for differential privacy in genomics sense (phenotypic differential privacy): http://www.cell.com/cell-systems/fulltext/S2405-4712(16)30121-1 “
Accurate Prediction of Contact Numbers for Multi-Spanning Helical Membrane Proteins
November 25, 2017Accurate Prediction of Contact Numbers for Multi-Spanning Helical #MembraneProteins – via #NeuralNetwork w/ dropout
http://pubs.ACS.org/doi/abs/10.1021/acs.jcim.5b00517 In turn, this can enable accurate prediction of the rotation of TM helices & then the 3D #StructurePrediction of the whole protein
Atomic structure of the entire mammalian mitochondrial complex I | Nature
November 25, 2017Atomic structure of the entire mammalian mitochondrial complex I https://www.Nature.com/articles/nature19794 Synthesizing #cryoEM w/ (high-FP) cross-linking data to gets a 3.9A structure w/ 78 helices
Fiedorczuk, K., Letts, J.A., Degliesposti, G., Kaszuba, K., Skehel, M., Sazanov, L.A. (2016) Atomic structure of the entire mammalian mitochondrial complex I. Nature 538; 406-410.
related to:
• Letts, J.A., Fiedorczuk, K., Sazanov, L.A. (2016) The architecture of respiratory supercomplexes. Nature 537; 644-648.
Chromatin states define tumour-specific T cell dysfunction and reprogramming | Nature
November 19, 2017PatternMarkers & GWCoGAPS for novel data-driven biomarkers via whole transcriptome NMF | Bioinformatics | Oxford Academic
November 19, 2017Quantifying the local resolution of cryo-EM density maps | Nature Methods
November 14, 2017Quantifying the local resolution of #cryoEM density maps
https://www.Nature.com/articles/nmeth.2727 “Theory…based on the following idea: a L Angstrom feature exists at a pt…if a 3D local sinusoid of wavelength L is statistically detectable above noise at that point.”
QT:{{”
We propose a mathematical theory and an efficient algorithm for measuring local resolution that address all of the above limitations. The theory (Online Methods) is based on the following idea: a λ-Å feature exists at a point in the volume if a three-dimensional (3D) local sinusoid of wavelength λ is statistically detectable above noise at that point. A likelihood-ratio hypothesis test of the local sinusoid versus noise can detect this feature at a given P value (typically P = 0.05). We define the local resolution at a point as the smallest λ at which the local sinusoid is detectable, and we account for multiple testing with an FDR procedure.
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