Browsing by Subject "microarray"

Now showing 1 - 6 of 6
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    Assessing copy number aberrations and copy neutral loss of heterozygosity across the genome as best practice: An evidence based review of clinical utility from the cancer genomics consortium (CGC) working group for myelodysplastic syndrome, myelodysplastic/myeloproliferative and myeloproliferative neoplasms
    (Elsevier, 2018) Kanagal-Shamanna, Rashmi; Hodge, Jennelle C.; Tucker, Tracy; Shetty, Shashi; Yenamandra, Ashwini; Dixon-McIver, Amanda; Bryke, Christine; Huxley, Emma; Lennon, Patrick A.; Raca, Gordana; Xu, Xinjie; Jeffries, Sally; Quintero-Rivera, Fabiola; Greipp, Patricia T.; Slovak, Marilyn L.; Iqbal, M. Anwar; Fang, Min; Medical and Molecular Genetics, School of Medicine
    Multiple studies have demonstrated the utility of chromosomal microarray (CMA) testing to identify clinically significant copy number alterations (CNAs) and copy-neutral loss-of-heterozygosity (CN-LOH) in myeloid malignancies. However, guidelines for integrating CMA as a standard practice for diagnostic evaluation, assessment of prognosis and predicting treatment response are still lacking. CMA has not been recommended for clinical work-up of myeloid malignancies by the WHO 2016 or the NCCN 2017 guidelines but is a suggested test by the European LeukaemiaNet 2013 for the diagnosis of primary myelodysplastic syndrome (MDS). The Cancer Genomics Consortium (CGC) Working Group for Myeloid Neoplasms systematically reviewed peer-reviewed literature to determine the power of CMA in (1) improving diagnostic yield, (2) refining risk stratification, and (3) providing additional genomic information to guide therapy. In this manuscript, we summarize the evidence base for the clinical utility of array testing in the workup of MDS, myelodysplastic/myeloproliferative neoplasms (MDS/MPN) and myeloproliferative neoplasms (MPN). This review provides a list of recurrent CNAs and CN-LOH noted in this disease spectrum and describes the clinical significance of the aberrations and how they complement gene mutation findings by sequencing. Furthermore, for new or suspected diagnosis of MDS or MPN, we present suggestions for integrating genomic testing methods (CMA and mutation testing by next generation sequencing) into the current standard-of-care clinical laboratory testing (karyotype, FISH, morphology, and flow).
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    Early transcriptome profile of goat peripheral blood mononuclear cells (PBMCs) infected with peste des petits ruminant's vaccine virus (Sungri/96) revealed induction of antiviral response in an interferon independent manner
    (Elsevier, 2019-06) Manjunath, Siddappa; Saxena, Shikha; Mishra, Bina; Santra, Lakshman; Sahu, Amit Ranjan; Wani, Sajad Ahmed; Tiwari, Ashok Kumar; Mishra, Bishnu Prasad; Singh, Raj Kumar; Janga, Sarath Chandra; Kumar, Gandham Ravi; BioHealth Informatics, School of Informatics and Computing
    Sungri/96 vaccine strain is considered the most potent vaccine providing long-term immunity against peste des petits ruminants (PPR) in India. Previous studies in our laboratory highlighted induction of robust antiviral response in an interferon independent manner at 48 h and 120 h post infection (p.i.). However, immune response at the earliest time point 6 h p.i. (time taken to complete one PPRV life cycle), in PBMCs infected with Sungri/96 vaccine virus has not been investigated. This study was taken up to understand the global gene expression profiling of goat PBMCs after Sungri/96 PPRV vaccine strain infection at 6 h post infection (p.i.). A total of 1926 differentially expressed genes (DEGs) were identified with 616 - upregulated and 1310 - downregulated. TLR7/TLR3, IRF7/IRF1, ISG20, IFIT1/IFIT2, IFITM3, IL27 and TREX1 were identified as key immune sensors and antiviral candidate genes. Interestingly, type I interferons (IFNα/β) were not differentially expressed at this time point as well. TREX1, an exonuclease which inhibits type I interferons at the early stage of virus infection was found to be highly upregulated. IL27, an important antiviral host immune factor was significantly upregulated. ISG20, an antiviral interferon induced gene with exonuclease activity specific to ssRNA viruses was highly expressed. Functional profiling of DEGs showed significant enrichment of immune system processes with 233 genes indicating initiation of immune defense response in host cells. Protein interaction network showed important innate immune molecules in the immune network with high connectivity. The study highlights important immune and antiviral genes at the earliest time point.
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    Model-based Comparative Prediction of Transcription-Factor Binding Motifs in Anabolic Responses in Bone.
    (Elsevier, 2007) Chen, Andy B.; Hamamura, Kazunori; Wang, Guohua; Xing, Weirong; Mohan, Subburaman; Yokota, Hiroki; Liu, Yunlong; Department of Biomedical Engineering, School of Engineering and Technology
    Understanding the regulatory mechanism that controls the alteration of global gene expression patterns continues to be a challenging task in computational biology. We previously developed an ant algorithm, a biologically-inspired computational technique for microarray data, and predicted putative transcription-factor binding motifs (TFBMs) through mimicking interactive behaviors of natural ants. Here we extended the algorithm into a set of web-based software, Ant Modeler, and applied it to investigate the transcriptional mechanism underlying bone formation. Mechanical loading and administration of bone morphogenic proteins (BMPs) are two known treatments to strengthen bone. We addressed a question: Is there any TFBM that stimulates both “anabolic responses of mechanical loading” and “BMP-mediated osteogenic signaling”? Although there is no significant overlap among genes in the two responses, a comparative model-based analysis suggests that the two independent osteogenic processes employ common TFBMs, such as a stress responsive element and a motif for peroxisome proliferator-activated receptor (PPAR). The post-modeling in vitro analysis using mouse osteoblast cells supported involvements of the predicted TFBMs such as PPAR, Ikaros 3, and LMO2 in response to mechanical loading. Taken together, the results would be useful to derive a set of testable hypotheses and examine the role of specific regulators in complex transcriptional control of bone formation.
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    Role of miR-222-3p in c-Src-Mediated Regulation of Osteoclastogenesis
    (MDPI, 2016-02-16) Takigawa, Shinya; Chen, Andy; Wan, Qiaoqiao; Na, Sungsoo; Sudo, Akihiro; Yokota, Hiroki; Hamamura, Kazunori; Biomedical Engineering, School of Engineering and Technology
    MicroRNAs (miRNAs) are small non-coding RNAs that play a mostly post-transcriptional regulatory role in gene expression. Using RAW264.7 pre-osteoclast cells and genome-wide expression analysis, we identified a set of miRNAs that are involved in osteoclastogenesis. Based on in silico analysis, we specifically focused on miR-222-3p and evaluated its role in osteoclastogenesis. The results show that the inhibitor of miR-222-3p upregulated the mRNA levels of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and tartrate-resistant acid phosphatase (TRAP), while its mimicking agent downregulated their mRNA levels. Western blot analysis showed that its inhibitor increased the protein levels of TRAP and cathepsin K, while its mimicking agent decreased their levels. Genome-wide mRNA expression analysis in the presence and absence of receptor activator of nuclear factor κ-B ligand (RANKL) predicted c-Src as a potential regulatory target of miR-222-3p. Live cell imaging using a fluorescence resonance energy transfer (FRET) technique revealed that miR-222-3p acted as an inhibitor of c-Src activity, and a partial silencing of c-Src suppressed RANKL-induced expression of TRAP and cathepsin K, as well as the number of multi-nucleated osteoclasts and their pit formation. Collectively, the study herein demonstrates that miR-222-3p serves as an inhibitor of osteoclastogenesis and c-Src mediates its inhibition of cathepsin K and TRAP.
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    Sources of transcription variation in Plasmodium falciparum
    (Elsevier, 2022-10) Turnbull , Lindsey B.; Button-Simons , Katrina A.; Agbayani, Nestor; Ferdig, Michael T.; Pediatrics, School of Medicine
    Variation in transcript abundance can contribute to both short-term environmental response and long-term evolutionary adaptation. Most studies are designed to assess differences in mean transcription levels and do not consider other potentially important and confounding sources of transcriptional variation. Detailed quantification of variation sources will improve our ability to detect and identify the mechanisms that contribute to genome-wide transcription changes that underpin adaptive responses. To quantify innate levels of expression variation, we measured mRNA levels for more than 5000 genes in the malaria parasite, Plasmodium falciparum, among clones derived from two parasite strains across biologically and experimentally replicated batches. Using a mixed effects model, we partitioned the total variation among four sources—between strain, within strain, environmental batch effects, and stochastic noise. We found 646 genes with significant variation attributable to at least one of these sources. These genes were categorized by their predominant variation source and further examined using gene ontology enrichment analysis to associate function with each source of variation. Genes with environmental batch effect and within strain transcript variation may contribute to phenotypic plasticity, while genes with between strain variation may contribute to adaptive responses and processes that lead to parasite strain-specific survival under varied conditions.
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    Transcriptional profiling of the ductus arteriosus: Comparison of rodent microarrays and human RNA sequencing
    (Elsevier, 2018) Yarboro, Michael T.; Durbin, Matthew D.; Herington, Jennifer L.; Shelton, Elaine L.; Zhang, Tao; Ebby, Cris G.; Stoller, Jason Z.; Clyman, Ronald I.; Reese, Jeff; Pediatrics, School of Medicine
    DA closure is crucial for the transition from fetal to neonatal life. This closure is supported by changes to the DA’s signaling and structural properties that distinguish it from neighboring vessels. Examining transcriptional differences between these vessels is key to identifying genes or pathways responsible for DA closure. Several microarray studies have explored the DA transcriptome in animal models but varied experimental designs have led to conflicting results. Thorough transcriptomic analysis of the human DA has yet to be performed. A clear picture of the DA transcriptome is key to guiding future research endeavors, both to allow more targeted treatments in the clinical setting, and to understand the basic biology of DA function. In this review, we use a cross-species cross-platform analysis to consider all available published rodent microarray data and novel human RNAseq data in order to provide high priority candidate genes for consideration in future DA studies.