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Combinatorial genomics

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https://www.readbyqxmd.com/read/28645527/inhibition-of-17beta-hydroxysteroid-dehydrogenase-type-7-modulates-breast-cancer-protein-profile-and-enhances-apoptosis-by-down-regulating-grp78
#1
Xiao-Qiang Wang, Juliette A Aka, Tang Li, Dan Xu, Charles J Doillon, Sheng-Xiang Lin
17beta-hydroxysteroid dehydrogenase type 7 (17β-HSD7) promotes breast cancer cell growth via dual-catalytic activity by modulating estradiol and DHT. Here, we clarified the expression pattern of 17β-HSD7 in postmenopausal luminal A type breast cancer with The Cancer Genome Atlas (TCGA) cohort. The impact of 17β-HSD7 inhibition on the proteome of MCF-7 cells was investigated and on cell apoptosis was revealed. MCF-7 cells were treated with an efficient inhibitor of 17β-HSD7 or with vehicle, and a differential proteomics study was performed using two-dimensional (2D) gel electrophoresis followed by mass spectrometry and ingenuity pathway analysis (IPA)...
June 20, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28630873/an-integrative-developmental-genomics-and-systems-biology-approach-to-identify-an-in-vivo-sox-trio-mediated-gene-regulatory-network-in-murine-embryos
#2
Wenqing Jean Lee, Sumantra Chatterjee, Sook Peng Yap, Siew Lan Lim, Xing Xing, Petra Kraus, Wenjie Sun, Xiaoming Hu, V Sivakamasundari, Hsiao Yun Chan, Prasanna R Kolatkar, Shyam Prabhakar, Thomas Lufkin
Embryogenesis is an intricate process involving multiple genes and pathways. Some of the key transcription factors controlling specific cell types are the Sox trio, namely, Sox5, Sox6, and Sox9, which play crucial roles in organogenesis working in a concerted manner. Much however still needs to be learned about their combinatorial roles during this process. A developmental genomics and systems biology approach offers to complement the reductionist methodology of current developmental biology and provide a more comprehensive and integrated view of the interrelationships of complex regulatory networks that occur during organogenesis...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28623575/from-genes-to-networks-characterizing-gene-regulatory-interactions-in-plants
#3
Kerstin Kaufmann, Dijun Chen
Plants, like other eukaryotes, have evolved complex mechanisms to coordinate gene expression during development, environmental response, and cellular homeostasis. Transcription factors (TFs), accompanied by basic cofactors and posttranscriptional regulators, are key players in gene-regulatory networks (GRNs). The coordinated control of gene activity is achieved by the interplay of these factors and by physical interactions between TFs and DNA. Here, we will briefly outline recent technological progress made to elucidate GRNs in plants...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28611825/epigenetic-combinatorial-patterns-predict-disease-variants
#4
Yu Zhang
Most genetic variants identified in genome-wide association studies are noncoding and are likely tagging nearby causal variants. It is a challenging task to pinpoint the precise locations of disease-causal variants and understand their functions in disease. A promising approach to improve fine mapping is to integrate the functional data currently available on hundreds of human tissues and cell types. Although there are several methods that use functional data to prioritize disease variants, they mainly use linear models, or equivalent naive likelihood-based models for prediction...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28600722/genetic-dissection-of-plant-growth-habit-in-chickpea
#5
Hari D Upadhyaya, Deepak Bajaj, Rishi Srivastava, Anurag Daware, Udita Basu, Shailesh Tripathi, Chellapilla Bharadwaj, Akhilesh K Tyagi, Swarup K Parida
A combinatorial genomics-assisted breeding strategy encompassing association analysis, genetic mapping and expression profiling is found most promising for quantitative dissection of complex traits in crop plants. The present study employed GWAS (genome-wide association study) using 24,405 SNPs (single nucleotide polymorphisms) obtained with genotyping-by-sequencing (GBS) of 92 sequenced desi and kabuli accessions of chickpea. This identified eight significant genomic loci associated with erect (E)/semi-erect (SE) vs...
June 9, 2017: Functional & Integrative Genomics
https://www.readbyqxmd.com/read/28592988/algorithms-for-computing-the-double-cut-and-join-distance-on-both-gene-order-and-intergenic-sizes
#6
Guillaume Fertin, Géraldine Jean, Eric Tannier
BACKGROUND: Combinatorial works on genome rearrangements have so far ignored the influence of intergene sizes, i.e. the number of nucleotides between consecutive genes, although it was recently shown decisive for the accuracy of inference methods (Biller et al. in Genome Biol Evol 8:1427-39, 2016; Biller et al. in Beckmann A, Bienvenu L, Jonoska N, editors. Proceedings of Pursuit of the Universal-12th conference on computability in Europe, CiE 2016, Lecture notes in computer science, vol 9709, Paris, France, June 27-July 1, 2016...
2017: Algorithms for Molecular Biology: AMB
https://www.readbyqxmd.com/read/28590847/new-genome-similarity-measures-based-on-conserved-gene-adjacencies
#7
Daniel Doerr, Luis Antonio B Kowada, Eloi Araujo, Shachi Deshpande, Simone Dantas, Bernard M E Moret, Jens Stoye
Many important questions in molecular biology, evolution, and biomedicine can be addressed by comparative genomic approaches. One of the basic tasks when comparing genomes is the definition of measures of similarity (or dissimilarity) between two genomes, for example, to elucidate the phylogenetic relationships between species. The power of different genome comparison methods varies with the underlying formal model of a genome. The simplest models impose the strong restriction that each genome under study must contain the same genes, each in exactly one copy...
June 2017: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
https://www.readbyqxmd.com/read/28589207/prediction-and-in-vitro-verification-of-potential-ctl-epitopes-conserved-among-prrsv-2-strains
#8
Simon Welner, Morten Nielsen, Michael Rasmussen, Søren Buus, Gregers Jungersen, Lars Erik Larsen
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is the causative agent of one of the most important porcine diseases with a high impact on animal health, welfare, and production economy. PRRSV exhibits a multitude of immunoevasive strategies that, in combination with a very high mutation rate, has hampered the development of safe and broadly protective vaccines. Aiming at a vaccine inducing an effective cytotoxic T cell response, a bioinformatics approach was taken to identify conserved PRRSV-derived peptides predicted to react broadly with common swine leukocyte antigen (SLA) class I alleles...
June 7, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28581336/challenges-and-progress-in-interpretation-of-non-coding-genetic-variants-associated-with-human-disease
#9
Yizhou Zhu, Cagdas Tazearslan, Yousin Suh
Genome-wide association studies have shown that the far majority of disease-associated variants reside in the non-coding regions of the genome, suggesting that gene regulatory changes contribute to disease risk. To identify truly causal non-coding variants and their affected target genes remains challenging but is a critical step to translate the genetic associations to molecular mechanisms and ultimately clinical applications. Here we review genomic/epigenomic resources and in silico tools that can be used to identify causal non-coding variants and experimental strategies to validate their functionalities...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28579515/chrombisim-interactive-chromatin-biclustering-using-a-simple-approach
#10
Nighat Noureen, Hafiz Muhammad Zohaib, Muhammad Abdul Qadir, Sahar Fazal
Combinatorial patterns of histone modifications sketch the epigenomic locale. Specific positions of these modifications in the genome are marked by the presence of such signals. Various methods highlight such patterns on global scale hence missing the local patterns which are the actual hidden combinatorics. We present ChromBiSim, an interactive tool for mining subsets of modifications from epigenomic profiles. ChromBiSim efficiently extracts biclusters with their genomic locations. It is the very first user interface based and multiple cell type handling tool for decoding the interplay of subsets of histone modifications combinations along their genomic locations...
June 1, 2017: Genomics
https://www.readbyqxmd.com/read/28574612/basal-cell-carcinoma-pathogenesis-and-therapy-involving-hedgehog-signaling-and-beyond
#11
Anshika Bakshi, Sandeep C Chaudhary, Mehtab Rana, Craig A Elmets, Mohammad Athar
Basal cell carcinoma (BCC) of the skin is driven by aberrant hedgehog signaling. Thus blocking this signaling pathway by small molecules such as vismodegib inhibits tumor growth. Primary cilium in the epidermal cells plays an integral role in the processing of hedgehog signaling related proteins. Recent genomic studies point to the involvement of additional genetic mutations that might be associated with the development of BCCs, suggesting significance of other signaling pathways, such as WNT, NOTCH, mTOR, and Hippo, aside from hedgehog in the pathogenesis of this human neoplasm...
June 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28572842/grid-based-stochastic-search-for-hierarchical-gene-gene-interactions-in-population-based-genetic-studies-of-common-human-diseases
#12
Jason H Moore, Peter C Andrews, Randal S Olson, Sarah E Carlson, Curt R Larock, Mario J Bulhoes, James P O'Connor, Ellen M Greytak, Steven L Armentrout
BACKGROUND: Large-scale genetic studies of common human diseases have focused almost exclusively on the independent main effects of single-nucleotide polymorphisms (SNPs) on disease susceptibility. These studies have had some success, but much of the genetic architecture of common disease remains unexplained. Attention is now turning to detecting SNPs that impact disease susceptibility in the context of other genetic factors and environmental exposures. These context-dependent genetic effects can manifest themselves as non-additive interactions, which are more challenging to model using parametric statistical approaches...
2017: BioData Mining
https://www.readbyqxmd.com/read/28559416/in-vitro-expansion-of-mouse-primordial-germ-cell-like-cells-recapitulates-an-epigenetic-blank-slate
#13
Hiroshi Ohta, Kazuki Kurimoto, Ikuhiro Okamoto, Tomonori Nakamura, Yukihiro Yabuta, Hidetaka Miyauchi, Takuya Yamamoto, Yukiko Okuno, Masatoshi Hagiwara, Kenjiro Shirane, Hiroyuki Sasaki, Mitinori Saitou
The expansion of primordial germ cells (PGCs), the precursors for the oocytes and spermatozoa, is a key challenge in reproductive biology/medicine. Using a chemical screening exploiting PGC-like cells (PGCLCs) induced from mouse embryonic stem cells (ESCs), we here identify key signaling pathways critical for PGCLC proliferation. We show that the combinatorial application of Forskolin and Rolipram, which stimulate cAMP signaling via different mechanisms, expands PGCLCs up to ~50-fold in culture. The expanded PGCLCs maintain robust capacity for spermatogenesis, rescuing the fertility of infertile mice...
May 30, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28530678/the-complex-genetics-of-hypoplastic-left-heart-syndrome
#14
Xiaoqin Liu, Hisato Yagi, Shazina Saeed, Abha S Bais, George C Gabriel, Zhaohan Chen, Kevin A Peterson, You Li, Molly C Schwartz, William T Reynolds, Manush Saydmohammed, Brian Gibbs, Yijen Wu, William Devine, Bishwanath Chatterjee, Nikolai T Klena, Dennis Kostka, Karen L de Mesy Bentley, Madhavi K Ganapathiraju, Phillip Dexheimer, Linda Leatherbury, Omar Khalifa, Anchit Bhagat, Maliha Zahid, William Pu, Simon Watkins, Paul Grossfeld, Stephen A Murray, George A Porter, Michael Tsang, Lisa J Martin, D Woodrow Benson, Bruce J Aronow, Cecilia W Lo
Congenital heart disease (CHD) affects up to 1% of live births. Although a genetic etiology is indicated by an increased recurrence risk, sporadic occurrence suggests that CHD genetics is complex. Here, we show that hypoplastic left heart syndrome (HLHS), a severe CHD, is multigenic and genetically heterogeneous. Using mouse forward genetics, we report what is, to our knowledge, the first isolation of HLHS mutant mice and identification of genes causing HLHS. Mutations from seven HLHS mouse lines showed multigenic enrichment in ten human chromosome regions linked to HLHS...
May 22, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28515787/a-computational-approach-for-the-functional-classification-of-the-epigenome
#15
Francesco Gandolfi, Anna Tramontano
BACKGROUND: In the last decade, advanced functional genomics approaches and deep sequencing have allowed large-scale mapping of histone modifications and other epigenetic marks, highlighting functional relationships between chromatin organization and genome function. Here, we propose a novel approach to explore functional interactions between different epigenetic modifications and extract combinatorial profiles that can be used to annotate the chromatin in a finite number of functional classes...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28513710/are-highly-morphed-peptide-frameworks-lurking-silently-in-microbial-genomes-valuable-as-next-generation-antibiotic-scaffolds
#16
Christopher T Walsh
Antibiotics are a therapeutic class that, once deployed, select for resistant bacterial pathogens and so shorten their useful life cycles. As a consequence new versions of antibiotics are constantly needed. Among the antibiotic natural products, morphed peptide scaffolds, converting conformationally mobile, short-lived linear peptides into compact, rigidified small molecule frameworks, act on a wide range of bacterial targets. Advances in bacterial genome mining, biosynthetic gene cluster prediction and expression, and mass spectroscopic structure analysis suggests many more peptides, modified both in side chains and peptide backbones, await discovery...
May 17, 2017: Natural Product Reports
https://www.readbyqxmd.com/read/28511883/a-prostate-cancer-nimbosus-genomic-instability-and-schlap1-dysregulation-underpin-aggression-of-intraductal-and-cribriform-subpathologies
#17
Melvin L K Chua, Winnie Lo, Melania Pintilie, Jure Murgic, Emilie Lalonde, Vinayak Bhandari, Osman Mahamud, Anuradha Gopalan, Charlotte F Kweldam, Geert J L H van Leenders, Esther I Verhoef, Agnes Marije Hoogland, Julie Livingstone, Alejandro Berlin, Alan Dal Pra, Alice Meng, Junyan Zhang, Michèle Orain, Valérie Picard, Hélène Hovington, Alain Bergeron, Louis Lacombe, Yves Fradet, Bernard Têtu, Victor E Reuter, Neil Fleshner, Michael Fraser, Paul C Boutros, Theodorus H van der Kwast, Robert G Bristow
BACKGROUND: Intraductal carcinoma (IDC) and cribriform architecture (CA) represent unfavorable subpathologies in localized prostate cancer. We recently showed that IDC shares a clonal ancestry with the adjacent glandular adenocarcinoma. OBJECTIVE: We investigated for the co-occurrence of "aggression" factors, genomic instability and hypoxia, and performed gene expression profiling of these tumors. DESIGN, SETTING, AND PARTICIPANTS: A total of 1325 men were treated for localized prostate cancer from four academic institutions (University Health Network, CHU de Québec-Université Laval, Memorial Sloan Kettering Cancer Center [MSKCC], and Erasmus Medical Center)...
May 13, 2017: European Urology
https://www.readbyqxmd.com/read/28508547/functional-phosphatome-requirement-for-protein-homeostasis-networked-mitochondria-and-sarcomere-structure-in-c-%C3%A2-elegans-muscle
#18
Susann Lehmann, Joseph J Bass, Thomas F Barratt, Mohammed Z Ali, Nathaniel J Szewczyk
BACKGROUND: Skeletal muscle is central to locomotion and metabolic homeostasis. The laboratory worm Caenorhabditis elegans has been developed into a genomic model for assessing the genes and signals that regulate muscle development and protein degradation. Past work has identified a receptor tyrosine kinase signalling network that combinatorially controls autophagy, nerve signal to muscle to oppose proteasome-based degradation, and extracellular matrix-based signals that control calpain and caspase activation...
May 15, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/28499350/transcription-factor-associated-combinatorial-epigenetic-pattern-reveals-higher-transcriptional-activity-of-tcf7l2-regulated-intragenic-enhancers
#19
Qi Liu, Russell Bonneville, Tianbao Li, Victor X Jin
BACKGROUND: Recent studies have suggested that combinations of multiple epigenetic modifications are essential for controlling gene expression. Despite numerous computational approaches have been developed to decipher the combinatorial epigenetic patterns or "epigenetic code", none of them has explicitly addressed the relationship between a specific transcription factor (TF) and the patterns. METHODS: Here, we developed a novel computational method, T-cep, for annotating chromatin states associated with a specific TF...
May 12, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28499008/rippminer-a-bioinformatics-resource-for-deciphering-chemical-structures-of-ripps-based-on-prediction-of-cleavage-and-cross-links
#20
Priyesh Agrawal, Shradha Khater, Money Gupta, Neetu Sain, Debasisa Mohanty
Ribosomally synthesized and post-translationally modified peptides (RiPPs) constitute a rapidly growing class of natural products with diverse structures and bioactivities. We have developed RiPPMiner, a novel bioinformatics resource for deciphering chemical structures of RiPPs by genome mining. RiPPMiner derives its predictive power from machine learning based classifiers, trained using a well curated database of more than 500 experimentally characterized RiPPs. RiPPMiner uses Support Vector Machine to distinguish RiPP precursors from other small proteins and classify the precursors into 12 sub-classes of RiPPs...
May 12, 2017: Nucleic Acids Research
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