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https://www.readbyqxmd.com/read/29457794/recon3d-enables-a-three-dimensional-view-of-gene-variation-in-human-metabolism
#1
Elizabeth Brunk, Swagatika Sahoo, Daniel C Zielinski, Ali Altunkaya, Andreas Dräger, Nathan Mih, Francesco Gatto, Avlant Nilsson, German Andres Preciat Gonzalez, Maike Kathrin Aurich, Andreas Prlić, Anand Sastry, Anna D Danielsdottir, Almut Heinken, Alberto Noronha, Peter W Rose, Stephen K Burley, Ronan M T Fleming, Jens Nielsen, Ines Thiele, Bernhard O Palsson
Genome-scale network reconstructions have helped uncover the molecular basis of metabolism. Here we present Recon3D, a computational resource that includes three-dimensional (3D) metabolite and protein structure data and enables integrated analyses of metabolic functions in humans. We use Recon3D to functionally characterize mutations associated with disease, and identify metabolic response signatures that are caused by exposure to certain drugs. Recon3D represents the most comprehensive human metabolic network model to date, accounting for 3,288 open reading frames (representing 17% of functionally annotated human genes), 13,543 metabolic reactions involving 4,140 unique metabolites, and 12,890 protein structures...
February 19, 2018: Nature Biotechnology
https://www.readbyqxmd.com/read/29444205/ssbio-a-python-framework-for-structural-systems-biology
#2
Nathan Mih, Elizabeth Brunk, Ke Chen, Edward Catoiu, Anand Sastry, Erol Kavvas, Jonathan M Monk, Zhen Zhang, Bernhard O Palsson, Alfonso Valencia
Summary: Working with protein structures at the genome-scale has been challenging in a variety of ways. Here, we present ssbio, a Python package that provides a framework to easily work with structural information in the context of genome-scale network reconstructions, which can contain thousands of individual proteins. The ssbio package provides an automated pipeline to construct high quality genomescale models with protein structures (GEM-PROs), wrappers to popular third-party programs to compute associated protein properties, and methods to visualize and annotate structures directly in Jupyter notebooks, thus lowering the barrier of linking 3D structural data with established systems workflows...
February 12, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29438494/artificial-intelligence-in-drug-combination-therapy
#3
Igor F Tsigelny
Currently, the development of medicines for complex diseases requires the development of combination drug therapies. It is necessary because in many cases, one drug cannot target all necessary points of intervention. For example, in cancer therapy, a physician often meets a patient having a genomic profile including more than five molecular aberrations. Drug combination therapy has been an area of interest for a while, for example the classical work of Loewe devoted to the synergism of drugs was published in 1928-and it is still used in calculations for optimal drug combinations...
February 9, 2018: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/29435408/a-putative-rna-binding-protein-from-plasmodium-vivax-apicoplast
#4
Sofía M García-Mauriño, Antonio Díaz-Quintana, Francisco Rivero-Rodríguez, Isabel Cruz-Gallardo, Christian Grüttner, Marian Hernández-Vellisca, Irene Díaz-Moreno
Malaria is caused by Apicomplexa protozoans from the Plasmodium genus entering the bloodstream of humans and animals through the bite of the female mosquitoes. The annotation of the Plasmodium vivax genome revealed a putative RNA binding protein (apiRBP) that was predicted to be trafficked into the apicoplast, a plastid organelle unique to Apicomplexa protozoans. Although a 3D structural model of the apiRBP corresponds to a noncanonical RNA recognition motif with an additional C-terminal α-helix (α3), preliminary protein production trials were nevertheless unsuccessful...
February 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29433549/thinking-big-rheumatology-how-to-make-functional-genomics-data-work-for-you
#5
REVIEW
Deborah R Winter
High-throughput sequencing assays have become an increasingly common part of biological research across multiple fields. Even as the resulting sequences pile up in public databases, it is not always obvious how to make use of these data sets. Functional genomics offers approaches to integrate these "big" data into our understanding of rheumatic diseases. This review aims to provide a primer on thinking about big data from functional genomics in the context of rheumatology, using examples from the field's literature as well as the author's own work to illustrate the execution of functional genomics research...
February 12, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/29432181/three-classes-of-recurrent-dna-break-clusters-in-brain-progenitors-identified-by-3d-proximity-based-break-joining-assay
#6
Pei-Chi Wei, Cheng-Sheng Lee, Zhou Du, Bjoern Schwer, Yuxiang Zhang, Jennifer Kao, Jeffrey Zurita, Frederick W Alt
We recently discovered 27 recurrent DNA double-strand break (DSB) clusters (RDCs) in mouse neural stem/progenitor cells (NSPCs). Most RDCs occurred across long, late-replicating RDC genes and were found only after mild inhibition of DNA replication. RDC genes share intriguing characteristics, including encoding surface proteins that organize brain architecture and neuronal junctions, and are genetically implicated in neuropsychiatric disorders and/or cancers. RDC identification relies on high-throughput genome-wide translocation sequencing (HTGTS), which maps recurrent DSBs based on their translocation to "bait" DSBs in specific chromosomal locations...
February 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29431585/calculation-of-3d-genome-structures-for-comparison-of-chromosome-conformation-capture-experiments-with-microscopy-an-evaluation-of-single-cell-hi-c-protocols
#7
David Lando, Tim J Stevens, Srinjan Basu, Ernest D Laue
Single-cell chromosome conformation capture approaches are revealing the extent of cell-to-cell variability in the organization and packaging of genomes. These single-cell methods, unlike their multi-cell counterparts, allow straightforward computation of realistic chromosome conformations that may be compared and combined with other, independent, techniques to study 3D structure. Here we discuss how single-cell Hi-C and subsequent 3D genome structure determination allows comparison with data from microscopy...
February 12, 2018: Nucleus
https://www.readbyqxmd.com/read/29430346/identification-and-molecular-characterization-of-dof-transcription-factor-gene-family-preferentially-expressed-in-developing-spikes-of-eleusine-coracana-l
#8
Supriya Gupta, Rajesh Kumar Pathak, Sanjay Mohan Gupta, Vikram Singh Gaur, N K Singh, Anil Kumar
We report 48 putative DNA binding with one finger (Dof) TF genes from genome and transcriptome data of finger millet (Eleusine coracana L.; FM), involved in plant developmental process. To characterize seed-specific Dof genes, transcript profiles of 32 EcDof identified from transcriptome data of developing spikes of FM genotypes were further analyzed in different tissues (root, stem, and leaf) and developmental stages of spikes (S1, S2, S3, and S4) in two FM genotypes [GE1437 (low protein genotype; LPG) and GE3885 (high protein genotype; HPG)]...
February 2018: 3 Biotech
https://www.readbyqxmd.com/read/29428417/juicebox-js-provides-a-cloud-based-visualization-system-for-hi-c-data
#9
James T Robinson, Douglass Turner, Neva C Durand, Helga Thorvaldsdóttir, Jill P Mesirov, Erez Lieberman Aiden
Contact mapping experiments such as Hi-C explore how genomes fold in 3D. Here, we introduce Juicebox.js, a cloud-based web application for exploring the resulting datasets. Like the original Juicebox application, Juicebox.js allows users to zoom in and out of such datasets using an interface similar to Google Earth. Juicebox.js also has many features designed to facilitate data reproducibility and sharing. Furthermore, Juicebox.js encodes the exact state of the browser in a shareable URL. Creating a public browser for a new Hi-C dataset does not require coding and can be accomplished in under a minute...
February 5, 2018: Cell Systems
https://www.readbyqxmd.com/read/29423548/detection-and-genetic-characterization-of-bovine-kobuvirus-from-calves-in-egypt
#10
Fakry F Mohamed, Shimaa M G Mansour, Ahmed Orabi, Iman E El-Araby, Terry Fei Fan Ng, Sunil K Mor, Sagar M Goyal
Kobuviruses are small non-enveloped RNA viruses that probably cause diarrhea in cattle and swine. Since its discovery in 2003, few studies have addressed bovine kobuvirus (BKoV; a species of Aichivirus B) infections. BKoV has been reported in Europe, Asia, and South America, suggesting a worldwide distribution. To investigate the presence of BKoV in Egypt, 36 fecal specimens from diarrheic calves in two different Egyptian provinces (Cairo and Sharkia) were screened by RT-PCR and 24 (66.7%) were found positive for BKoV...
February 8, 2018: Archives of Virology
https://www.readbyqxmd.com/read/29419817/investigation-of-the-spatial-structure-and-interactions-of-the-genome-at-sub-kilobase-pair-resolution-using-t2c
#11
Petros Kolovos, Rutger W W Brouwer, Christel E M Kockx, Michael Lesnussa, Nick Kepper, Jessica Zuin, A M Ali Imam, Harmen J G van de Werken, Kerstin S Wendt, Tobias A Knoch, Wilfred F J van IJcken, Frank Grosveld
Chromosome conformation capture (3C) and its derivatives (e.g., 4C, 5C and Hi-C) are used to analyze the 3D organization of genomes. We recently developed targeted chromatin capture (T2C), an inexpensive method for studying the 3D organization of genomes, interactomes and structural changes associated with gene regulation, the cell cycle, and cell survival and development. Here, we present the protocol for T2C based on capture, describing all experimental steps and bio-informatic tools in full detail. T2C offers high resolution, a large dynamic interaction frequency range and a high signal-to-noise ratio...
March 2018: Nature Protocols
https://www.readbyqxmd.com/read/29411909/gene-expression-profiles-of-the-meniscus-avascular-phenotype-a-guide-for-meniscus-tissue-engineering
#12
Shawn P Grogan, Stuart F Duffy, Chantal Pauli, Martin K Lotz, Darryl D D'Lima
Avascular (Avas) meniscus regeneration remains a challenge, which is partly a consequence of our limited knowledge of the cells that maintain this tissue region. In this study, we utilized microarrays to characterize gene expression profiles of intact human Avas meniscus tissue and of cells following culture expansion. Using these data, we examined various 3D culture conditions to redifferentiate Avas cells toward the tissue phenotype. RNA was isolated from either the tissue directly or following cell isolation and 2 weeks in monolayer culture...
February 7, 2018: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/29410074/the-relative-composition-of-actin-isoforms-regulates-cell-surface-biophysical-features-and-cellular-behaviors
#13
Xin Xie, Muhammedin Deliorman, Mohammad A Qasaimeh, Piergiorgio Percipalle
BACKGROUND: Cell surface mechanics is able to physically and biomechanically affect cell shape and motility, vesicle trafficking and actin dynamics. The biophysical properties of cell surface are strongly influenced by cytoskeletal elements. In mammals, tissue-specific expression of six actin isoforms is thought to confer differential biomechanical properties. However, the relative contribution of actin isoforms to cell surface properties is not well understood. Here, we sought to investigate whether and how the composition of endogenous actin isoforms directly affects the biomechanical features of cell surface and cellular behavior...
February 1, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29408992/reconstructing-spatial-organizations-of-chromosomes-through-manifold-learning
#14
Guangxiang Zhu, Wenxuan Deng, Hailin Hu, Rui Ma, Sai Zhang, Jinglin Yang, Jian Peng, Tommy Kaplan, Jianyang Zeng
Decoding the spatial organizations of chromosomes has crucial implications for studying eukaryotic gene regulation. Recently, chromosomal conformation capture based technologies, such as Hi-C, have been widely used to uncover the interaction frequencies of genomic loci in a high-throughput and genome-wide manner and provide new insights into the folding of three-dimensional (3D) genome structure. In this paper, we develop a novel manifold learning based framework, called GEM (Genomic organization reconstructor based on conformational Energy and Manifold learning), to reconstruct the three-dimensional organizations of chromosomes by integrating Hi-C data with biophysical feasibility...
February 2, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29397498/genetic-mapping-of-a-novel-recessive-allele-for-non-glaucousness-in-wild-diploid-wheat-aegilops-tauschii-implications-for-the-evolution-of-common-wheat
#15
Ryo Nishijima, Chisa Tanaka, Kentaro Yoshida, Shigeo Takumi
Cuticular wax on the aerial surface of plants has a protective function against many environmental stresses. The bluish-whitish appearance of wheat leaves and stems is called glaucousness. Most modern cultivars of polyploid wheat species exhibit the glaucous phenotype, while in a wild wheat progenitor, Ae. tauschii, both glaucous and non-glaucous accessions exist. Iw2, a wax inhibitor locus on the short arm of chromosome 2D, is the main contributor to this phenotypic variation in Ae. tauschii, and the glaucous/non-glaucous phenotype of Ae...
February 3, 2018: Genetica
https://www.readbyqxmd.com/read/29395927/genetic-regulation-of-the-2d-to-3d-growth-transition-in-the-moss-physcomitrella-patens
#16
Laura A Moody, Steven Kelly, Ester Rabbinowitsch, Jane A Langdale
One of the most important events in the history of life on earth was the colonization of land by plants; this transition coincided with and was most likely enabled by the evolution of 3-dimensional (3D) growth. Today, the diverse morphologies exhibited across the terrestrial biosphere arise from the differential regulation of 3D growth processes during development. In many plants, 3D growth is initiated during the first few divisions of the zygote, and therefore, the genetic basis cannot be dissected because mutants do not survive...
January 24, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29394376/direct-transfection-of-clonal-organoids-in-matrigel-microbeads-a-promising-approach-toward-organoid-based-genetic-screens
#17
Bastien Laperrousaz, Stephanie Porte, Sophie Gerbaud, Ville Härmä, Frédérique Kermarrec, Virginie Hourtane, Frédéric Bottausci, Xavier Gidrol, Nathalie Picollet-D'hahan
Organoid cultures in 3D matrices are relevant models to mimic the complex in vivo environment that supports cell physiological and pathological behaviors. For instance, 3D epithelial organoids recapitulate numerous features of glandular tissues including the development of fully differentiated acini that maintain apico-basal polarity with hollow lumen. Effective genetic engineering in organoids would bring new insights in organogenesis and carcinogenesis. However, direct 3D transfection on already formed organoids remains challenging...
January 31, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29391599/targeting-plk1-overcomes-t-dm1-resistance-via-cdk1-dependent-phosphorylation-and-inactivation-of-bcl-2-xl-in-her2-positive-breast-cancer
#18
Özge Saatci, Simone Borgoni, Özge Akbulut, Selvi Durmuş, Umar Raza, Erol Eyüpoğlu, Can Alkan, Aytekin Akyol, Özgür Kütük, Stefan Wiemann, Özgür Şahin
Trastuzumab-refractory, HER2 (human epidermal growth factor receptor 2)-positive breast cancer is commonly treated with trastuzumab emtansine (T-DM1), an antibody-drug conjugate of trastuzumab and the microtubule-targeting agent, DM1. However, drug response reduces greatly over time due to acquisition of resistance whose molecular mechanisms are mostly unknown. Here, we uncovered a novel mechanism of resistance against T-DM1 by combining whole transcriptome sequencing (RNA-Seq), proteomics and a targeted small interfering RNA (siRNA) sensitization screen for molecular level analysis of acquired and de novo T-DM1-resistant models of HER2-overexpressing breast cancer...
February 2, 2018: Oncogene
https://www.readbyqxmd.com/read/29385704/discovery-of-cryoprotective-activity-in-human-genome-derived-intrinsically-disordered-proteins
#19
Naoki Matsuo, Natsuko Goda, Kana Shimizu, Satoshi Fukuchi, Motonori Ota, Hidekazu Hiroaki
Intrinsically disordered proteins (IDPs) are an emerging phenomenon. They may have a high degree of flexibility in their polypeptide chains, which lack a stable 3D structure. Although several biological functions of IDPs have been proposed, their general function is not known. The only finding related to their function is the genetically conserved YSK₂ motif present in plant dehydrins. These proteins were shown to be IDPs with the YSK₂ motif serving as a core region for the dehydrins' cryoprotective activity...
January 30, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29385519/genomic-dissection-of-enhancers-uncovers-principles-of-combinatorial-regulation-and-cell-type-specific-wiring-of-enhancer-promoter-contacts
#20
Verena Thormann, Maika C Rothkegel, Robert Schöpflin, Laura V Glaser, Petar Djuric, Na Li, Ho-Ryun Chung, Kevin Schwahn, Martin Vingron, Sebastiaan H Meijsing
Genomic binding of transcription factors, like the glucocorticoid receptor (GR), is linked to the regulation of genes. However, as we show here, GR binding is a poor predictor of GR-dependent gene regulation even when taking the 3D organization of the genome into account. To connect GR binding sites to the regulation of genes in the endogenous genomic context, we turned to genome editing. By deleting GR binding sites, individually or in combination, we uncovered how cooperative interactions between binding sites contribute to the regulation of genes...
January 27, 2018: Nucleic Acids Research
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