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Combinatorial genomics

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https://www.readbyqxmd.com/read/29344882/detection-of-combinatorial-mutational-patterns-in-human-cancer-genomes-by-exclusivity-analysis
#1
Hua Tan, Xiaobo Zhou
Cancer genes may tend to mutate in a co-mutational or mutually exclusive manner in a tumor sample of a specific cancer, which constitute two known combinatorial mutational patterns for a given gene set. Previous studies have established that genes functioning in different signaling pathways can mutate in the same sample, i.e., a tumor from one patient, while genes operating in the same pathway are rarely mutated in the same cancer genome. Therefore, reliable identification of combinatorial mutational patterns of candidate cancer genes has important ramifications in inferring signaling network modules in a particular cancer type...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29330556/evolution-of-the-phosphatidylcholine-biosynthesis-pathways-in-green-algae-combinatorial-diversity-of-methyltransferases
#2
Takashi Hirashima, Masakazu Toyoshima, Takashi Moriyama, Naoki Sato
Phosphatidylcholine (PC) is one of the most common phospholipids in eukaryotes, although some green algae such as Chlamydomonas reinhardtii are known to lack PC. Recently, we detected PC in four species in the genus Chlamydomonas: C. applanata NIES-2202, C. asymmetrica NIES-2207, C. debaryana NIES-2212, and C. sphaeroides NIES-2242. To reveal the PC biosynthesis pathways in green algae and the evolutionary scenario involved in their diversity, we analyzed the PC biosynthesis genes in these four algae using draft genome sequences...
January 12, 2018: Journal of Molecular Evolution
https://www.readbyqxmd.com/read/29325558/systematic-target-function-annotation-of-human-transcription-factors
#3
Yong Fuga Li, Russ B Altman
BACKGROUND: Transcription factors (TFs), the key players in transcriptional regulation, have attracted great experimental attention, yet the functions of most human TFs remain poorly understood. Recent capabilities in genome-wide protein binding profiling have stimulated systematic studies of the hierarchical organization of human gene regulatory network and DNA-binding specificity of TFs, shedding light on combinatorial gene regulation. We show here that these data also enable a systematic annotation of the biological functions and functional diversity of TFs...
January 10, 2018: BMC Biology
https://www.readbyqxmd.com/read/29320559/characterization-of-the-naive-murine-antibody-repertoire-using-unamplified-high-throughput-sequencing
#4
Trisha A Rettig, Claire Ward, Bailey A Bye, Michael J Pecaut, Stephen K Chapes
Antibody specificity and diversity are generated through the enzymatic splicing of genomic gene segments within each B cell. Antibodies are heterodimers of heavy- and light-chains encoded on separate loci. We studied the antibody repertoire from pooled, splenic tissue of unimmunized, adult female C57BL/6J mice, using high-throughput sequencing (HTS) without amplification of antibody transcripts. We recovered over 90,000 heavy-chain and over 135,000 light-chain immunoglobulin sequences. Individual V-, D-, and J-gene segment usage was uniform among the three mouse pools, particularly in highly abundant gene segments, with low frequency V-gene segments not being detected in all pools...
2018: PloS One
https://www.readbyqxmd.com/read/29315387/a-validated-grna-library-for-crispr-cas9-targeting-of-the-human-glycosyltransferase-genome
#5
Yoshiki Narimatsu, Hiren J Joshi, Yang Zhang, Catarina Gomes, Yen-Hsi Chen, Flaminia Lorenzetti, Sanae Furukawa, Katrine Schjoldager, Lars Hansen, Henrik Clausen, Eric P Bennett, Hans H Wandall
Over 200 glycosyltransferases are involved in the orchestration of the biosynthesis of the human glycome , which is comprised of all glycan structures found on different glycoconjugates in cells. The glycome is vast, and despite advancements in analytic strategies it continues to be difficult to decipher biological roles of glycans with respect to specific glycan structures, type of glycoconjugate, particular glycoproteins, and distinct glycosites on proteins. In contrast to this, the number of glycosyltransferase genes involved in the biosynthesis of the human glycome is manageable, and the biosynthetic roles of most of these enzymes are defined or can be predicted with reasonable confidence...
January 5, 2018: Glycobiology
https://www.readbyqxmd.com/read/29288438/synthetic-biology-genome-mining-and-combinatorial-biosynthesis-of-nrps-derived-antibiotics-a-perspective
#6
Richard H Baltz
Combinatorial biosynthesis of novel secondary metabolites derived from nonribosomal peptide synthetases (NRPSs) has been in slow development for about a quarter of a century. Progress has been hampered by the complexity of the giant multimodular multienzymes. More recently, advances have been made on understanding the chemical and structural biology of these complex megaenzymes, and on learning the design rules for engineering functional hybrid enzymes. In this perspective, I address what has been learned about successful engineering of complex lipopeptides related to daptomycin, and discuss how synthetic biology and microbial genome mining can converge to broaden the scope and enhance the speed and robustness of combinatorial biosynthesis of NRPS-derived natural products for drug discovery...
December 29, 2017: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/29286469/generation-of-native-chromatin-immunoprecipitation-sequencing-libraries-for-nucleosome-density-analysis
#7
Alireza Lorzadeh, Rodrigo Lopez Gutierrez, Linda Jackson, Michelle Moksa, Martin Hirst
We present a modified native chromatin immunoprecipitation sequencing (ChIP-seq) experimental protocol compatible with a Gaussian mixture distribution based analysis methodology (nucleosome density ChIP-seq; ndChIP-seq) that enables the generation of combined measurements of micrococcal nuclease (MNase) accessibility with histone modification genome-wide. Nucleosome position and local density, and the posttranslational modification of their histone subunits, act in concert to regulate local transcription states...
December 12, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29277870/whole-genome-duplication-in-plants-implications-for-evolutionary-analysis
#8
David Sankoff, Chunfang Zheng
The recurrent cycle of whole genome duplication (WGD) followed by massive duplicate gene loss (fractionation) differentiates plant evolutionary history from that of most other phylogenetic domains, where WGD has occurred relatively rarely, even on an evolutionary time scale. We discuss the mechanism of WGD and its biological consequences. We survey the prevalence of WGD in the flowering plants. We outline some of the major kinds of combinatorial optimization problems arising in computational biology for analyzing WGD...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29274663/long-noncoding-rna-in-cancer-wiring-signaling-circuitry
#9
REVIEW
Chunru Lin, Liuqing Yang
Long noncoding RNAs (lncRNAs), which are encoded by a vast less explored region of the human genome, may hold missing drivers of cancer and have gained attention recently as a potentially crucial layer of cancer cell regulation. lncRNAs are aberrantly expressed in a broad spectrum of cancers, and they play key roles in promoting and maintaining tumor initiation and progression, demonstrating their clinical potential as biomarkers and therapeutic targets. Recent discoveries have revealed that lncRNAs act as key signal transduction mediators in cancer signaling pathways by interacting with proteins, RNA, and lipids...
December 20, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/29274630/molecular-tools-for-pathway-engineering-in-saccharomyces-cerevisiae
#10
REVIEW
Pamela B Besada-Lombana, Tami L McTaggart, Nancy A Da Silva
Molecular tools for the regulation of protein expression in Saccharomyces cerevisiae have contributed to rapid advances in pathway engineering for this yeast. This review considers new and enhanced additions to this toolbox, focusing on experimental approaches to modulate enzyme synthesis and enzyme fate. Methods for genome engineering, regulation of transcription, post-translational protein localization, and combinatorial screening and sensing in S. cerevisiae are highlighted, and promising new approaches are introduced...
December 20, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29243807/microrna-as-a-systemic-intervention-in-the-specific-breast-cancer-subtypes-with-c-myc-impacts-introducing-subtype-based-appraisal-tool
#11
REVIEW
Vida Pourteimoor, Mahdi Paryan, Samira Mohammadi-Yeganeh
Breast cancer is indisputably a heterogeneous disease, in which a formidable combination of definitely dis-regulated C-MYC and microRNA (miRNA) profiles along with other factors are responsible to generate a specific type of breast cancer. C-MYC as a master regulator of more than 20,000 genes can modify the expression of genes underlying to perform diverse conflicting functional frameworks. The functional spectra of miRNA in the new areas of the evolution of cell behaviors are identified. Here, we endeavor to summarize some recent advances of miRNA applications that can be recruited as combinatorial targeted therapy for patients with breast cancer...
December 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29236736/functions-for-fission-yeast-splicing-factors-spslu7-and-spprp18-in-alternative-splice-site-choice-and-stress-specific-regulated-splicing
#12
Geetha Melangath, Titash Sen, Rakesh Kumar, Pushpinder Bawa, Subha Srinivasan, Usha Vijayraghavan
Budding yeast spliceosomal factors ScSlu7 and ScPrp18 interact and mediate intron 3'ss choice during second step pre-mRNA splicing. The fission yeast genome with abundant multi-intronic transcripts, degenerate splice signals and SR proteins is an apt unicellular fungal model to deduce roles for core spliceosomal factors in alternative splice-site choice, intron retention and to study the cellular implications of regulated splicing. From our custom microarray data we deduce a stringent reproducible subset of S...
2017: PloS One
https://www.readbyqxmd.com/read/29235467/in-situ-functional-dissection-of-rna-cis-regulatory-elements-by-multiplex-crispr-cas9-genome-engineering
#13
Qianxin Wu, Quentin R V Ferry, Toni A Baeumler, Yale S Michaels, Dimitrios M Vitsios, Omer Habib, Roland Arnold, Xiaowei Jiang, Stefano Maio, Bruno R Steinkraus, Marta Tapia, Paolo Piazza, Ni Xu, Georg A Holländer, Thomas A Milne, Jin-Soo Kim, Anton J Enright, Andrew R Bassett, Tudor A Fulga
RNA regulatory elements (RREs) are an important yet relatively under-explored facet of gene regulation. Deciphering the prevalence and functional impact of this post-transcriptional control layer requires technologies for disrupting RREs without perturbing cellular homeostasis. Here we describe genome-engineering based evaluation of RNA regulatory element activity (GenERA), a clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 platform for in situ high-content functional analysis of RREs...
December 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29229819/discovery-of-the-leinamycin-family-of-natural-products-by-mining-actinobacterial-genomes
#14
Guohui Pan, Zhengren Xu, Zhikai Guo, Hindra, Ming Ma, Dong Yang, Hao Zhou, Yannick Gansemans, Xiangcheng Zhu, Yong Huang, Li-Xing Zhao, Yi Jiang, Jinhua Cheng, Filip Van Nieuwerburgh, Joo-Won Suh, Yanwen Duan, Ben Shen
Nature's ability to generate diverse natural products from simple building blocks has inspired combinatorial biosynthesis. The knowledge-based approach to combinatorial biosynthesis has allowed the production of designer analogs by rational metabolic pathway engineering. While successful, structural alterations are limited, with designer analogs often produced in compromised titers. The discovery-based approach to combinatorial biosynthesis complements the knowledge-based approach by exploring the vast combinatorial biosynthesis repertoire found in Nature...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29222760/computational-prediction-of-synthetic-lethals-in-genome-scale-metabolic-models-using-fast-sl
#15
Karthik Raman, Aditya Pratapa, Omkar Mohite, Shankar Balachandran
In this chapter, we describe Fast-SL, an in silico approach to predict synthetic lethals in genome-scale metabolic models. Synthetic lethals are sets of genes or reactions where only the simultaneous removal of all genes or reactions in the set abolishes growth of an organism. In silico approaches to predict synthetic lethals are based on Flux Balance Analysis (FBA), a popular constraint-based analysis method based on linear programming. FBA has been shown to accurately predict the viability of various genome-scale metabolic models...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29222305/biology-of-cns-lymphoma-and-the-potential-of-novel-agents
#16
REVIEW
James L Rubenstein
Primary and secondary CNS lymphomas are aggressive brain tumors that pose an immense challenge to define in terms of molecular pathogenesis, as well as to effectively treat. During the past 10 years improvements in survival have been achieved with the implementation of anti-CD20 immunotherapy and optimization of dose-intensive consolidation strategies. The applications of whole-exome sequencing, comparative genomic hybridization, transcriptional profiling, and examination of the tumor microenvironment, particularly in the context of clinical investigation, provide insights that create a roadmap for the development and implementation of novel targeted agents for this disease...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29218903/coalitional-game-theory-as-a-promising-approach-to-identify-candidate-autism-genes
#17
Anika Gupta, Min Woo Sun, Kelley Marie Paskov, Nate Tyler Stockham, Jae-Yoon Jung, Dennis Paul Wall
Despite mounting evidence for the strong role of genetics in the phenotypic manifestation of Autism Spectrum Disorder (ASD), the specific genes responsible for the variable forms of ASD remain undefined. ASD may be best explained by a combinatorial genetic model with varying epistatic interactions across many small effect mutations. Coalitional or cooperative game theory is a technique that studies the combined effects of groups of players, known as coalitions, seeking to identify players who tend to improve the performance--the relationship to a specific disease phenotype--of any coalition they join...
2018: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/29216191/transcription-factors-coregulators-and-epigenetic-marks-are-linearly-correlated-and-highly-redundant
#18
Tobias Ahsendorf, Franz-Josef Müller, Ved Topkar, Jeremy Gunawardena, Roland Eils
The DNA microstates that regulate transcription include sequence-specific transcription factors (TFs), coregulatory complexes, nucleosomes, histone modifications, DNA methylation, and parts of the three-dimensional architecture of genomes, which could create an enormous combinatorial complexity across the genome. However, many proteins and epigenetic marks are known to colocalize, suggesting that the information content encoded in these marks can be compressed. It has so far proved difficult to understand this compression in a systematic and quantitative manner...
2017: PloS One
https://www.readbyqxmd.com/read/29212445/chromosome-structures-reduction-of-certain-problems-with-unequal-gene-content-and-gene-paralogs-to-integer-linear-programming
#19
Vassily Lyubetsky, Roman Gershgorin, Konstantin Gorbunov
BACKGROUND: Chromosome structure is a very limited model of the genome including the information about its chromosomes such as their linear or circular organization, the order of genes on them, and the DNA strand encoding a gene. Gene lengths, nucleotide composition, and intergenic regions are ignored. Although highly incomplete, such structure can be used in many cases, e.g., to reconstruct phylogeny and evolutionary events, to identify gene synteny, regulatory elements and promoters (considering highly conserved elements), etc...
December 6, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/29211822/insights-from-resolving-protein-dna-interactions-at-near-base-pair-resolution
#20
Bryan J Venters
One of the central goals in molecular biology is to understand how cell-type-specific expression patterns arise through selective recruitment of RNA polymerase II (Pol II) to a subset of gene promoters. Pol II needs to be recruited to a precise genomic position at the proper time to produce messenger RNA from a DNA template. Ostensibly, transcription is a relatively simple cellular process; yet, experimentally measuring and then understanding the combinatorial possibilities of transcriptional regulators remain a daunting task...
December 2, 2017: Briefings in Functional Genomics
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