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Expression genomic integration

Laura Brueckner, Joris van Arensbergen, Waseem Akhtar, Ludo Pagie, Bas van Steensel
BACKGROUND: Chromatin proteins control gene activity in a concerted manner. We developed a high-throughput assay to study the effects of the local chromatin environment on the regulatory activity of a protein of interest. The assay combines a previously reported multiplexing strategy based on barcoded randomly integrated reporters with Gal4-mediated tethering. We applied the assay to Drosophila heterochromatin protein 1a (HP1a), which is mostly known as a repressive protein but has also been linked to transcriptional activation...
2016: Epigenetics & Chromatin
Juan I Fuxman Bass, Carles Pons, Lucie Kozlowski, John S Reece-Hoyes, Shaleen Shrestha, Amy D Holdorf, Akihiro Mori, Chad L Myers, Albertha Jm Walhout
Transcription factors (TFs) play a central role in controlling spatiotemporal gene expression and the response to environmental cues. A comprehensive understanding of gene regulation requires integrating physical protein-DNA interactions (PDIs) with TF regulatory activity, expression patterns, and phenotypic data. Although great progress has been made in mapping PDIs using chromatin immunoprecipitation, these studies have only characterized ~10% of TFs in any metazoan species. The nematode C. elegans has been widely used to study gene regulation due to its compact genome with short regulatory sequences...
October 24, 2016: Molecular Systems Biology
Bing Zheng, Jun Liu, Jianlei Gu, Jing Du, Lin Wang, Shengli Gu, Juan Cheng, Jun Yang, Hui Lu
BACKGROUND: A key challenge in thyroid carcinoma is preoperatively diagnosing malignant thyroid nodules. A novel diagnostic test that measures the expression of a 3-gene signature (DPP4, SCG5 and CA12) has demonstrated promise in thyroid carcinoma assessment. However, more reliable prediction methods combining clinical features with genomic signatures with high accuracy, good stability and low cost are needed. METHODOLOGY/PRINCIPAL FINDINGS: 25 clinical information were recorded in 771 patients...
2016: PloS One
Jonathan M Mudge, Jennifer Harrow
A genome sequence is worthless if it cannot be deciphered; therefore, efforts to describe - or 'annotate' - genes began as soon as DNA sequences became available. Whereas early work focused on individual protein-coding genes, the modern genomic ocean is a complex maelstrom of alternative splicing, non-coding transcription and pseudogenes. Scientists - from clinicians to evolutionary biologists - need to navigate these waters, and this has led to the design of high-throughput, computationally driven annotation projects...
October 24, 2016: Nature Reviews. Genetics
Benjamin Wooden, Nicolas Goossens, Yujin Hoshida, Scott L Friedman
Technologies such as genome sequencing, gene expression profiling, proteomic and metabolomic analyses, electronic medical records, and patient-reported health information have produced large amounts of data, from various populations, cell types, and disorders (big data). However, these data must be integrated and analyzed if they are to produce models or concepts about physiologic function or mechanisms of pathogenesis. Many of these data are available to the public, allowing researchers anywhere to search for markers of specific biologic processes or therapeutic targets for specific diseases or patient types...
October 20, 2016: Gastroenterology
Feixiong Cheng, Junfei Zhao, Ariella B Hanker, Monica Red Brewer, Carlos L Arteaga, Zhongming Zhao
PURPOSE: Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in human breast cancer. Furthermore, PIK3CA mutations are commonly associated with resistance to anti-epidermal growth factor receptor 2 (HER2) or anti-estrogen receptor (ER) agents in HER2 or ER positive (HER2(+)/ER(+)) breast cancer. Hence, deciphering the underlying mechanisms of PIK3CA mutations in HER2(+)/ER(+) breast cancer would provide novel insights into elucidating resistance to anti-HER2/ER therapies...
October 22, 2016: Breast Cancer Research and Treatment
Hui Dong, Hao Sun, Jianping Zheng
With the development of large-scale biologic databases, precision medicine is becoming a frontier in biomedical research. As a main focus of precision medicine study, cancer has been widely accepted as a disease born out of inherited genetic variations or accumulating genomic damage. At the single-cell level, microfluidics or lab-on-a-chip technology for cancer study is an emerging tool for improving risk assessment, diagnostic categories and therapeutic strategies. This work presents a multi-layer microchip for single-cell gene expression profiling...
December 1, 2016: Talanta
Lei Shi, Wenfa Zhang, Fagui Zou, Lihua Mei, Gang Wu, Yong Teng
BACKGROUND: Hepatocellular carcinoma (HCC) has very high prevalence and associated-mortality. However, targeted therapies that are currently used in clinical practice for HCC have certain limitations, in part because of the lack of reliable and clinically applicable biomarkers that can be used for diagnosis and prognosis assessments and for the surveillance of treatment effectiveness. METHODS: Meta-analysis was used to analyze the integrated microarray data for global identification of a set of robust biomarkers for HCC...
October 21, 2016: BMC Cancer
Chaoyun Hao, Zhiqiang Xia, Rui Fan, Lehe Tan, Lisong Hu, Baoduo Wu, Huasong Wu
BACKGROUND: Piper nigrum L., or "black pepper", is an economically important spice crop in tropical regions. Black pepper production is markedly affected by foot rot disease caused by Phytophthora capsici, and genetic improvement of black pepper is essential for combating foot rot diseases. However, little is known about the mechanism of anti- P. capsici in black pepper. The molecular mechanisms underlying foot rot susceptibility were studied by comparing transcriptome analysis between resistant (Piper flaviflorum) and susceptible (Piper nigrum cv...
October 21, 2016: BMC Genomics
Sergi Sayols, Denise Scherzinger, Holger Klein
BACKGROUND: PCR clonal artefacts originating from NGS library preparation can affect both genomic as well as RNA-Seq applications when protocols are pushed to their limits. In RNA-Seq however the artifactual reads are not easy to tell apart from normal read duplication due to natural over-sequencing of highly expressed genes. Especially when working with little input material or single cells assessing the fraction of duplicate reads is an important quality control step for NGS data sets...
October 21, 2016: BMC Bioinformatics
Ruifeng Liu, Xueping Yu, Anders Wallqvist
Chemical toxicity is conventionally evaluated in animal models. However, animal models are resource intensive; moreover, they face ethical and scientific challenges because the outcomes obtained by animal testing may not correlate with human responses. To develop an alternative method for assessing chemical toxicity, we investigated the feasibility of using chemical-induced genome-wide expression changes in cultured human cells to predict the potential of a chemical to cause specific organ injuries in humans...
October 21, 2016: Chemical Research in Toxicology
Ashton A Connor, Robert E Denroche, Gun Ho Jang, Lee Timms, Sangeetha N Kalimuthu, Iris Selander, Treasa McPherson, Gavin W Wilson, Michelle A Chan-Seng-Yue, Ivan Borozan, Vincent Ferretti, Robert C Grant, Ilinca M Lungu, Eithne Costello, William Greenhalf, Daniel Palmer, Paula Ghaneh, John P Neoptolemos, Markus Buchler, Gloria Petersen, Sarah Thayer, Michael A Hollingsworth, Alana Sherker, Daniel Durocher, Neesha Dhani, David Hedley, Stefano Serra, Aaron Pollett, Michael H A Roehrl, Prashant Bavi, John M S Bartlett, Sean Cleary, Julie M Wilson, Ludmil B Alexandrov, Malcolm Moore, Bradly G Wouters, John D McPherson, Faiyaz Notta, Lincoln D Stein, Steven Gallinger
Importance: Outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) remain poor. Advances in next-generation sequencing provide a route to therapeutic approaches, and integrating DNA and RNA analysis with clinicopathologic data may be a crucial step toward personalized treatment strategies for this disease. Objective: To classify PDAC according to distinct mutational processes, and explore their clinical significance. Design, Setting, and Participants: We performed a retrospective cohort study of resected PDAC, using cases collected between 2008 and 2015 as part of the International Cancer Genome Consortium...
October 20, 2016: JAMA Oncology
Yongsheng Bai, Lizhong Ding, Steve Baker, Jenny M Bai, Ethan Rath, Feng Jiang, Jianghong Wu, Hui Jiang, Gary Stuart
BACKGROUND: MicroRNAs (miRNA) are short nucleotides that interact with their target genes through 3' untranslated regions (UTRs). The Cancer Genome Atlas (TCGA) harbors an increasing amount of cancer genome data for both tumor and normal samples. However, there are few visualization tools focusing on concurrently displaying important relationships and attributes between miRNAs and mRNAs of both cancer tumor and normal samples. Moreover, a deep investigation of miRNA-mRNA target and biological relationships across multiple cancer types by integrating web-based analysis has not been thoroughly conducted...
October 6, 2016: BMC Bioinformatics
Carol H Miao
Current treatment of hemophilia A (HemA) patients with repeated infusions of factor VIII (FVIII; abbreviated as F8 in constructs) is costly, inconvenient, and incompletely effective. In addition, approximately 25 % of treated patients develop anti-factor VIII immune responses. Gene therapy that can achieve long-term phenotypic correction without the complication of anti-factor VIII antibody formation is highly desired. Lentiviral vector (LV)-mediated gene transfer into hematopoietic stem cells (HSCs) results in stable integration of FVIII gene into the host genome, leading to persistent therapeutic effect...
2016: Thrombosis Journal
James West, W Warren Gill
Genome editing in large animals has tremendous practical applications, from more accurate models for medical research through improved animal welfare and production efficiency. Although genetic modification in large animals has a 30 year history, until recently technical issues limited its utility. The original methods - pronuclear injection and integrating viruses - were plagued with problems associated with low efficiency, silencing, poor regulation of gene expression, and variability associated with random integration...
June 2016: Journal of Equine Veterinary Science
Mark A Applebaum, Aashish R Jha, Clara Kao, Kyle M Hernandez, Gillian DeWane, Helen R Salwen, Alexandre Chlenski, Marija Dobratic, Christopher J Mariani, Lucy A Godley, Nanduri Prabhakar, Kevin White, Barbara E Stranger, Susan L Cohn
Neuroblastoma is notable for its broad spectrum of clinical behavior ranging from spontaneous regression to rapidly progressive disease. Hypoxia is well known to confer a more aggressive phenotype in neuroblastoma. We analyzed transcriptome data from diagnostic neuroblastoma tumors and hypoxic neuroblastoma cell lines to identify genes whose expression levels correlate with poor patient outcome and are involved in the hypoxia response. By integrating a diverse set of transcriptome datasets, including those from neuroblastoma patients and neuroblastoma derived cell lines, we identified nine genes (SLCO4A1, ENO1, HK2, PGK1, MTFP1, HILPDA, VKORC1, TPI1, and HIST1H1C) that are up-regulated in hypoxia and whose expression levels are correlated with poor patient outcome in three independent neuroblastoma cohorts...
October 17, 2016: Oncotarget
Silvia Dal Santo, Alberto Palliotti, Sara Zenoni, Giovanni Battista Tornielli, Marianna Fasoli, Paola Paci, Sergio Tombesi, Tommaso Frioni, Oriana Silvestroni, Andrea Bellincontro, Claudio d'Onofrio, Fabiola Matarese, Matteo Gatti, Stefano Poni, Mario Pezzotti
BACKGROUND: Grapevine (Vitis vinifera L.) is an economically important crop with a wide geographical distribution, reflecting its ability to grow successfully in a range of climates. However, many vineyards are located in regions with seasonal drought, and these are often predicted to be global climate change hotspots. Climate change affects the entire physiology of grapevine, with strong effects on yield, wine quality and typicity, making it difficult to produce berries of optimal enological quality and consistent stability over the forthcoming decades...
October 20, 2016: BMC Genomics
Lydia Edjekouane, Samira Benhadjeba, Maïka Jangal, Hubert Fleury, Nicolas Gévry, Euridice Carmona, André Tremblay
Chromosomal and genome abnormalities at the 3p21.3 locus are frequent events linked to epithelial cancers, including ovarian and breast cancers. Genes encoded in the 3p21.3 cluster include HYAL1, HYAL2 and HYAL3 members of hyaluronidases involved in the breakdown of hyaluronan, an abundant component of the vertebrate extracellular matrix. However, the transcriptional regulation of HYAL genes is poorly defined. Here, we identified the estrogen receptor ERα as a negative regulator of HYAL1 expression in breast cancer cells...
October 13, 2016: Oncotarget
Masayuki Sano, Minoru Iijima, Manami Ohtaka, Mahito Nakanishi
Tissue-specific control of gene expression is an invaluable tool for studying various biological processes and medical applications. Efficient regulatory systems have been utilized to control transgene expression in various types of DNA viral or integrating viral vectors. However, existing regulatory systems are difficult to transfer into negative-strand RNA virus vector platforms because of significant differences in their transcriptional machineries. In this study, we developed a novel strategy for regulating transgene expression mediated by a cytoplasmic RNA vector based on a replication-defective and persistent Sendai virus (SeVdp)...
2016: PloS One
Kun Yang, Yun Gao, Mingfu Yang, Zuoshang Xu, Qian Chen
Because the function of most non-coding (nc) RNAs is unknown, Cre-lox transgenic mice are useful tools to determine their functions in a tissue or developmental stage-specific manner. However, the technology faces challenges because expression of ncRNA-transgene lacks protein product. No antibody or peptide-tag can be used to trace ncRNA expression in mouse tissues in real time. Furthermore, transgene integration at different locus or orientations in the genome may result in recombination of genomic fragments in the Cre-lox system...
October 20, 2016: Connective Tissue Research
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