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"Essential gene

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https://www.readbyqxmd.com/read/28730479/analysis-of-drug-resistance-using-kinome-wide-functional-screens
#1
Katherine R Singleton, Keith T Earley, Lynn E Heasley
The clinical success of tyrosine kinase inhibitors specific for BCR-ABL-, EGFR-, ALK-, and ROS1-driven cancers continues to spur the quest to match specific oncogene-defined tumor types with an appropriate molecularly targeted therapy. Unfortunately, responses to these agents are not durable with intrinsic or acquired resistance limiting benefit. Additionally, efforts to identify the appropriate targets of new drugs have focused on nonfunctional assays such as large-scale sequencing for somatic mutations or analysis of gene copy number...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28718810/dna2-an-important-player-in-dna-damage-response-or-just-another-dna-maintenance-protein
#2
REVIEW
Elzbieta Pawłowska, Joanna Szczepanska, Janusz Blasiak
The human DNA2 (DNA replication helicase/nuclease 2) protein is expressed in both the nucleus and mitochondria, where it displays ATPase-dependent nuclease and helicase activities. DNA2 plays an important role in the removing of long flaps in DNA replication and long-patch base excision repair (LP-BER), interacting with the replication protein A (RPA) and the flap endonuclease 1 (FEN1). DNA2 can promote the restart of arrested replication fork along with Werner syndrome ATP-dependent helicase (WRN) and Bloom syndrome protein (BLM)...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28717159/the-essential-genomic-landscape-of-the-commensal-bifidobacterium-breve-ucc2003
#3
Lorena Ruiz, Francesca Bottacini, Christine J Boinett, Amy K Cain, Mary O'Connell-Motherway, Trevor D Lawley, Douwe van Sinderen
Bifidobacteria are common gut commensals with purported health-promoting effects. This has encouraged scientific research into bifidobacteria, though recalcitrance to genetic manipulation and scarcity of molecular tools has hampered our knowledge on the precise molecular determinants of their health-promoting attributes and gut adaptation. To overcome this problem and facilitate functional genomic analyses in bifidobacteria, we created a large Tn5 transposon mutant library of the commensal Bifidobacterium breve UCC2003 that was further characterized by means of a Transposon Directed Insertion Sequencing (TraDIS) approach...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715411/a-curated-genome-scale-metabolic-model-of-bordetella-pertussis-metabolism
#4
Nick Fyson, Jerry King, Thomas Belcher, Andrew Preston, Caroline Colijn
The Gram-negative bacterium Bordetella pertussis is the causative agent of whooping cough, a serious respiratory infection causing hundreds of thousands of deaths annually worldwide. There are effective vaccines, but their production requires growing large quantities of B. pertussis. Unfortunately, B. pertussis has relatively slow growth in culture, with low biomass yields and variable growth characteristics. B. pertussis also requires a relatively expensive growth medium. We present a new, curated flux balance analysis-based model of B...
July 17, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28714028/identification-of-potential-target-genes-associated-with-the-pathogenesis-of-osteoarthritis-using-microarray-based-analysis
#5
Meng Li, Liqiang Zhi, Zhi Zhang, Weiguo Bian, Yusheng Qiu
The aim of the present study was to investigate the molecular circuitry of osteoarthritis (OA) and identify more potential target genes for OA treatment. Microarray data of GSE32317 was downloaded from the National Center for Biotechnology Information Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified in samples of synovial membrane from patients with early stage of knee OA (OA_Early) and late stage of knee OA (OA_End) that were compared with healthy specimens. Bioinformatics analysis was applied to analyze the significant functions and pathways that were enriched by the common DEGs identified in OA_Early and OA_End samples...
July 5, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28709640/genome-wide-identification-of-genes-essential-for-podocyte-cytoskeletons-based-on-single-cell-rna%C3%A2-sequencing
#6
Yuqiu Lu, Yuting Ye, Wenduona Bao, Qianqian Yang, Jinquan Wang, Zhihong Liu, Shaolin Shi
Gene expression differs substantially among individual cells of the same type. We speculate that genes that are expressed in all but a portion of cells of a given cell type would be likely essential and required for either the cell survival (housekeeping) or for the cell type's unique structure and function, enabling the organism to survive. Here, we performed RNA-seq of 20 mouse podocytes using the Fluidigm C1 system and identified 335 genes that were expressed in all of them. Among them, 239 genes were also expressed in mesangial and endothelial cells and were involved in energy metabolism, protein synthesis, etc...
July 11, 2017: Kidney International
https://www.readbyqxmd.com/read/28708996/functional-profiling-of-a-plasmodium-genome-reveals-an-abundance-of-essential-genes
#7
Ellen Bushell, Ana Rita Gomes, Theo Sanderson, Burcu Anar, Gareth Girling, Colin Herd, Tom Metcalf, Katarzyna Modrzynska, Frank Schwach, Rowena E Martin, Michael W Mather, Geoffrey I McFadden, Leopold Parts, Gavin G Rutledge, Akhil B Vaidya, Kai Wengelnik, Julian C Rayner, Oliver Billker
The genomes of malaria parasites contain many genes of unknown function. To assist drug development through the identification of essential genes and pathways, we have measured competitive growth rates in mice of 2,578 barcoded Plasmodium berghei knockout mutants, representing >50% of the genome, and created a phenotype database. At a single stage of its complex life cycle, P. berghei requires two-thirds of genes for optimal growth, the highest proportion reported from any organism and a probable consequence of functional optimization necessitated by genomic reductions during the evolution of parasitism...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28701701/systematic-discovery-of-genetic-modulation-by-jumonji-histone-demethylases-in-drosophila
#8
Nevine A Shalaby, Raheel Sayed, Qiao Zhang, Shane Scoggin, Susan Eliazer, Adrian Rothenfluh, Michael Buszczak
Jumonji (JmjC) domain proteins influence gene expression and chromatin organization by way of histone demethylation, which provides a means to regulate the activity of genes across the genome. JmjC proteins have been associated with many human diseases including various cancers, developmental and neurological disorders, however, the shared biology and possible common contribution to organismal development and tissue homeostasis of all JmjC proteins remains unclear. Here, we systematically tested the function of all 13 Drosophila JmjC genes...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28700943/a-role-for-mitochondrial-translation-in-promotion-of-viability-in-k-ras-mutant-cells
#9
Timothy D Martin, Danielle R Cook, Mei Yuk Choi, Mamie Z Li, Kevin M Haigis, Stephen J Elledge
Activating mutations in the KRAS oncogene are highly prevalent in tumors, especially those of the colon, lung, and pancreas. To better understand the genetic dependencies that K-Ras mutant cells rely upon for their growth, we employed whole-genome CRISPR loss-of-function screens in two isogenic pairs of cell lines. Since loss of essential genes is uniformly toxic in CRISPR-based screens, we also developed a small hairpin RNA (shRNA) library targeting essential genes. These approaches uncovered a large set of proteins whose loss results in the selective reduction of K-Ras mutant cell growth...
July 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28684554/trans-splicing-enhances-translational-efficiency-in-c-elegans
#10
Yu-Fei Yang, Xiaoqing Zhang, Xuehua Ma, Taolan Zhao, Qiushi Sun, Qing Huan, Shaohuan Wu, Zhuo Du, Wenfeng Qian
Translational efficiency is subject to extensive regulation. However, the factors influencing such regulation are poorly understood. In Caenorhabditis elegans, ~62% genes are trans-spliced to a specific spliced leader (SL1), which replaces part of the native 5' untranslated region (5' UTR). Given the pivotal role 5' UTR plays in the regulation of translational efficiency, we hypothesized that SL1 trans-splicing functions to regulate translational efficiency. With genome-wide analysis on Ribo-seq data, polysome profiling experiments, and CRISPR-Cas9-based genetic manipulation of trans-splicing sites, we found four lines of evidence in support of this hypothesis...
July 6, 2017: Genome Research
https://www.readbyqxmd.com/read/28683752/tnseqdiff-identification-of-conditionally-essential-genes-in-transposon-sequencing-studies
#11
Lili Zhao, Mark T Anderson, Weisheng Wu, Harry L T Mobley, Michael A Bachman
BACKGROUND: Tn-Seq is a high throughput technique for analysis of transposon mutant libraries to determine conditional essentiality of a gene under an experimental condition. A special feature of the Tn-seq data is that multiple mutants in a gene provides independent evidence to prioritize that gene as being essential. The existing methods do not account for this feature or rely on a high-density transposon library. Moreover, these methods are unable to accommodate complex designs. RESULTS: The method proposed here is specifically designed for the analysis of Tn-Seq data...
July 6, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28680150/virtual-screening-pharmacophore-development-and-structure-based-similarity-search-to-identify-inhibitors-against-ider-a-transcription-factor-of-mycobacterium-tuberculosis
#12
Akshay Rohilla, Garima Khare, Anil K Tyagi
ideR, an essential gene of Mycobacterium tuberculosis, is an attractive drug target as its conditional knockout displayed attenuated growth phenotype in vitro and in vivo. To the best of our knowledge, no inhibitors of IdeR are identified. We carried out virtual screening of NCI database against the IdeR DNA binding domain followed by inhibition studies using EMSA. Nine compounds exhibited potent inhibition with NSC 281033 (I-20) and NSC 12453 (I-42) exhibiting IC50 values of 2 µg/ml and 1 µg/ml, respectively...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28677146/genes-essential-for-phototrophic-growth-by-a-purple-alphaproteobacterium
#13
Jianming Yang, Liang Yin, Faith H Lessner, Ernesto S Nakayasu, Samuel H Payne, Kathryn R Fixen, Larry Gallagher, Caroline S Harwood
We used Tn-seq to identify genes essential for phototrophic growth by the purple bacterium Rhodopseudomonas palustris. We identified 167 genes required for anaerobic growth on acetate in light, 35 of which are annotated as photosynthesis genes. We verified the essentiality of many of these genes by analyzing the phenotypes of independently generated mutants that had altered pigmentation. We also identified three genes, two possibly involved in biogenesis of the membrane-bound photosynthetic apparatus and one for phosphadidylcholine biosynthesis, that were not known to be essential for phototrophic growth...
July 5, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28675450/synthetic-essentiality-targeting-tumor-suppressor-deficiencies-in-cancer
#14
REVIEW
Di Zhao, Ronald A DePinho
In this review, we summarize recent work exploring a novel conceptual approach termed "synthetic essentiality" as a means for targeting specific tumor suppressor gene deficiencies in cancer. With the aid of extensive publically available cancer genome and clinical databases, "synthetic essentiality" could be utilized to identify synthetic essential genes, which might be occasionally deleted in some cancers but almost always retained in the context of a specific tumor suppressor deficiency. Synthetic essentiality expands the existing concepts for therapeutic strategies, including oncogene addiction, tumor maintenance, synthetic, and collateral lethality, to provide a framework for the discovery of cancer-specific vulnerabilities...
July 4, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28674803/efficient-depletion-of-essential-gene-products-for-loss-of-function-studies-in-embryonic-stem-cells
#15
Soizik Berlivet, Isabelle Hmitou, Hélène Picaud, Matthieu Gérard
The development of the CRISPR/Cas9 technology has provided powerful methods to target genetic alterations. However, investigating the function of genes essential for cell survival remains problematic, because genetic ablation of these genes results in cell death. As a consequence, cells recombined at the targeted gene and fully depleted of the gene product cannot be obtained. RNA interference is well suited for the study of essential genes, but this approach often results in a partial depletion of the targeted gene product, which can lead to misinterpretations...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28674003/genome-sequence-of-a-diabetes-prone-rodent-reveals-a-mutation-hotspot-around-the-parahox-gene-cluster
#16
Adam D Hargreaves, Long Zhou, Josef Christensen, Ferdinand Marlétaz, Shiping Liu, Fang Li, Peter Gildsig Jansen, Enrico Spiga, Matilde Thye Hansen, Signe Vendelbo Horn Pedersen, Shameek Biswas, Kyle Serikawa, Brian A Fox, William R Taylor, John Frederick Mulley, Guojie Zhang, R Scott Heller, Peter W H Holland
The sand rat Psammomys obesus is a gerbil species native to deserts of North Africa and the Middle East, and is constrained in its ecology because high carbohydrate diets induce obesity and type II diabetes that, in extreme cases, can lead to pancreatic failure and death. We report the sequencing of the sand rat genome and discovery of an unusual, extensive, and mutationally biased GC-rich genomic domain. This highly divergent genomic region encompasses several functionally essential genes, and spans the ParaHox cluster which includes the insulin-regulating homeobox gene Pdx1...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28673247/de-novo-transcriptome-analysis-shows-differential-expression-of-genes-in-salivary-glands-of-edible-bird-s-nest-producing-swiftlets
#17
Q H Looi, H Amin, I Aini, M Zuki, A R Omar
BACKGROUND: Edible bird's nest (EBN), produced from solidified saliva secretions of specific swiftlet species during the breeding season, is one of the most valuable animal by-products in the world. The composition and medicinal benefits of EBN have been extensively studied, however, genomic and transcriptomic studies of the salivary glands of these birds have not been conducted. RESULTS: The study described the transcriptomes of salivary glands from three swiftlet species (28 samples) generated by RNASeq...
July 3, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28671706/an-integrative-machine-learning-strategy-for-improved-prediction-of-essential-genes-in-escherichia-coli-metabolism-using-flux-coupled-features
#18
Sutanu Nandi, Abhishek Subramanian, Ram Rup Sarkar
Prediction of essential genes helps to identify a minimal set of genes that are absolutely required for the appropriate functioning and survival of a cell. The available machine learning techniques for essential gene prediction have inherent problems, like imbalanced provision of training datasets, biased choice of the best model for a given balanced dataset, choice of a complex machine learning algorithm, and data-based automated selection of biologically relevant features for classification. Here, we propose a simple support vector machine-based learning strategy for the prediction of essential genes in Escherichia coli K-12 MG1655 metabolism that integrates a non-conventional combination of an appropriate sample balanced training set, a unique organism-specific genotype, phenotype attributes that characterize essential genes, and optimal parameters of the learning algorithm to generate the best machine learning model (the model with the highest accuracy among all the models trained for different sample training sets)...
July 3, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28661399/systematic-bacterialization-of-yeast-genes-identifies-a-near-universally-swappable-pathway
#19
Aashiq Hussain Kachroo, Jon Michael Laurent, Azat Akhmetov, Madelyn Szilagyi-Jones, Claire Darnell McWhite, Alice Zhao, Edward Michael Marcotte
Eukaryotes and prokaryotes last shared a common ancestor ~2 billion years ago, and while many present-day genes in these lineages predate this divergence, the extent to which these genes still perform their ancestral functions is largely unknown. To test principles governing retention of ancient function, we asked if prokaryotic genes could replace their essential eukaryotic orthologs. We systematically replaced essential genes in yeast by their 1:1 orthologs from Escherichia coli. After accounting for mitochondrial localization and alternative start codons, 31 out of 51 bacterial genes tested (61%) could complement a lethal growth defect and replace their yeast orthologs with minimal effects on growth rate...
June 29, 2017: ELife
https://www.readbyqxmd.com/read/28655737/evaluation-and-design-of-genome-wide-crispr-spcas9-knockout-screens
#20
Traver Hart, Amy Hin Yan Tong, Katie Chan, Jolanda Van Leeuwen, Ashwin Seetharaman, Michael Aregger, Megha Chandrashekhar, Nicole Hustedt, Sahil Seth, Avery Noonan, Andrea Habsid, Olga Sizova, Lyudmilla Nedyalkova, Ryan Climie, Leanne Tworzyanski, Keith Lawson, Maria Augusta Sartori, Sabriyeh Alibai, David Tieu, Sanna Masud, Patricia Mero, Alexander Weiss, Kevin R Brown, Matej Ušaj, Maximilian Billmann, Mahfuzur Rahman, Michael Costanzo, Chad L Myers, Brenda J Andrews, Charles Boone, Daniel Durocher, Jason Moffat
The adaptation of CRISPR/SpCas9 technology to mammalian cell lines is transforming the study of human functional genomics. Pooled libraries of CRISPR guide RNAs (gRNAs) targeting human protein-coding genes and encoded in viral vectors have been used to systematically create gene knockouts in a variety of human cancer and immortalized cell lines, in an effort to identify whether these knockouts cause cellular fitness defects. Previous work has shown that CRISPR screens are more sensitive and specific than pooled library shRNA screens in similar assays, but currently there exists significant variability across CRISPR library designs and experimental protocols...
June 27, 2017: G3: Genes—Genomes—Genetics
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