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1
Hall, James, Peter F. Ellis, Geoffrey J. Cary, Glenys Bishop, and Andrew L. Sullivan. "Long-distance spotting potential of bark strips of a ribbon gum (Eucalyptus viminalis)." International Journal of Wildland Fire 24, no. 8 (2015): 1109. http://dx.doi.org/10.1071/wf15031.
Повний текст джерелаАнотація:
Firebrands of ribbon bark eucalypt are notorious for igniting spotfires many kilometres ahead of a bushfire. However, no research to date has demonstrated that this bark type can sustain combustion at its terminal velocity for the travel time required. Fifty samples of shed bark of Eucalyptus viminalis of three distinct morphologies were ignited at one end and burned tethered in a vertical wind tunnel at air velocities approximating their terminal velocity. Mean terminal velocity and burnout time for ‘flat plates’, ‘simple cylinders’ and ‘internally convoluted cylinders’ were 5.4 m s–1 and 251 s; 5.2 m s–1 and 122 s; and 5.8 m s–1 and 429 s. The corresponding maximum burnout times were 785 s, 353 s and 1304 s. One internally convoluted cylinder flamed continuously and consumed its length of 368 mm in 271 s. The maximum burnout time for the internally convoluted cylinders is commensurate with a potential spotting distance exceeding 20 km given a mean wind speed during transport of 60 km h–1. This is the first study in which combustion times exceeding a few minutes have been recorded for this bark morphology, and thus provides some corroboration of the notoriety for long-distance spotting.
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Ahlberg, Christopher. "Spotfire." ACM SIGMOD Record 25, no. 4 (December 1996): 25–29. http://dx.doi.org/10.1145/245882.245893.
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Wilkins, Charles L. "Books and Software: Data mining with Spotfire Pro 4.0." Analytical Chemistry 72, no. 15 (August 2000): 550 A. http://dx.doi.org/10.1021/ac0028797.
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Gomez, H. L., M. A. Chavez, D. C. Doval, S. Franco, M. Arbushites, M. S. Berger, M. A. Casey, S. Stein, T. Zaks, and A. M. Martin. "Investigation of tumor biomarkers as response predictors in a monotherapy study with lapatinib (L) as a first line treatment in ErbB2 amplified women with breast cancer." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 10562. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.10562.
Повний текст джерелаАнотація:
10562 Background: Lapatinib is a potent inhibitor of both EGFR and HER2 tyrosine kinase activity. Results of the phase II trial EGF20009 in advanced or metastatic breast cancer (MBC) indicated an overall response rate of 24% to monotherapy L as first line (1L) treatment in 138 patients. In an effort to better define predictive biomarkers of response, we evaluated correlations between baseline tumor biomarker expression levels and clinical response to L. Methods: Response rate (RR) was defined as either complete response (CR) or partial response (PR). Tumor blocks were available on 118 patients from the time of most recent biopsy, and mRNA was extracted from 65 individual patient blocks for this preliminary analysis. Using qRT-PCR Taqman analysis, tumors were evaluated for expression of ERBB1- 4, PTEN, c-MYC, as well as two comparator genes for normalization. DecisionTree analysis using SpotFire software was performed to determine the genes most significantly associated with RR. Results: For the initial 65 patient samples analyzed, an elevation of ERBB2 expression was significantly associated with response to treatment with L (p=0.02) and a longer time to progression following treatment with L (p<0.0025). Furthermore, of the 17/65 responders in this preliminary study, SpotFire Decision Tree Analysis demonstrated that 16/17 (94%) who responded to L had a gene expression signature combining ERBB1, 2, and 3, which is currently being confirmed. No association was observed with ERBB4, PTEN and c-MYC in this preliminary analysis. Conclusion: This analysis suggests a correlation between elevated ERBB2 mRNA levels and both RR and TTP in patients treated with L as a 1L treatment. Analysis of the full set of samples (including genome-wide microarray analysis) is ongoing in an effort to determine biomarkers predictive of clinical activity beyond HER2. No significant financial relationships to disclose.
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Vaca, Mireya, Louie Naumovski, Chang-Heok Soh, and Jailene Leal. "Oncology early development technology to facilitate early analysis of safety and efficacy data." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e14116-e14116. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e14116.
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e14116 Background: The lack of a standard data review platform for the surveillance of early oncology trials led to the formation of a cross-functional initiative with the objective of creating a data surveillance framework that would provide clinical study teams with access to near real-time data in order to be able to generate fast insights into the safety and efficacy findings of oncology early development trials so that early signal detection or clinical proof-of-concept could take place. Methods: To determine the requirements that would drive the framework, the cross-functional team first conducted user interviews with study physicians to gather information on the types of tables, graphs, and visual outputs that would be most useful to the clinical study team, as well as most useful to re-create as a standard across the early oncology portfolio, focusing at this stage, on solid tumor trials using RECIST 1.1 for the efficacy output. Once these requirements were determined, specification details, including mock-ups of the visual output and guidelines to follow, were created. Programming and development of the pilot dashboard then began using R and Spotfire as the tools of choice. Results: The resulting dashboard branded “OED Fast Insights” included a standard set of pages composed of dynamic tables and graphs organized around 3 components: study disposition, disease response, and treatment-emergent adverse events. The output closely resembled tables and graphs the clinical study team were familiar with through statistical programming output using SAS. However, leveraging the interactive functionality of Spotfire allowed the team to produce dynamic tables and graphs that could be readily filtered by different pre-specified criteria (e.g. cohort, dose level, gender, lines of therapy, best overall response, type of cancer, biomarker status, etc.) or by subject or aggregate-level views, changed by different color indication, or adjusted in other ways by the user. The dynamic aspect of spider plots, waterfall plots, and swimmer lanes were of special interest in identifying early signal detection. Conclusions: The cross-functional initiative began in 2018 and by the end of 2019 the data surveillance framework was successfully scaled and rolled-out to the entire early oncology portfolio of existing trials utilizing RECIST 1.1 solid tumor criteria. The next phase of the initiative will be to extend the framework beyond RECIST 1.1 efficacy surveillance to include hematologic cancers.
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Wilson, Aaron C., Ioannis K. Moutsatsos, Gary Yu, Javier J. Pineda, Yan Feng, and Douglas S. Auld. "A Scalable Pipeline for High-Throughput Flow Cytometry." SLAS DISCOVERY: Advancing the Science of Drug Discovery 23, no. 7 (May 16, 2018): 708–18. http://dx.doi.org/10.1177/2472555218774770.
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Flow cytometry (FC) provides high-content data for a variety of applications, including phenotypic analysis of cell surface and intracellular markers, characterization of cell supernatant or lysates, and gene expression analysis. Historically, sample preparation, acquisition, and analysis have presented as a bottleneck for running such types of assays at scale. This article will outline the solutions that have been implemented at Novartis which have allowed high-throughput FC to be successfully conducted and analyzed for a variety of cell-based assays. While these experiments were generally conducted to measure phenotypic responses from a well-characterized and information-rich small molecular probe library known as the Mechanism-of-Action (MoA) Box, they are broadly applicable to any type of test sample. The article focuses on application of automated methods for FC sample preparation in 384-well assay plates. It also highlights a pipeline for analyzing large volumes of FC data, covering a visualization approach that facilitates review of screen-level data by dynamically embedding FlowJo (FJ) workspace images for each sample into a Spotfire file, directly linking them to the metric being observed. Finally, an application of these methods to a screen for MHC-I expression upregulators is discussed.
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Allen, E., Maikke Ohlson, David Finkelstein, Carrie Rosenberger, and Paul Thomas. "Transcriptional landscape of immune responses to naturally acquired influenza (HUM6P.248)." Journal of Immunology 194, no. 1_Supplement (May 1, 2015): 190.7. http://dx.doi.org/10.4049/jimmunol.194.supp.190.7.
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Abstract Several human population studies have sought to determine what components of the immune system confer protection to influenza infection. The aim of our study was to detect transcriptional changes contributing to the illness outcome in patients with naturally acquired influenza infection. Patients with naturally acquired influenza infection were recruited into a five year prospective, longitudinal cohort. Whole blood was sampled at day of enrollment (Day 0) and Days 3, 7, 10, and 28. Additionally, clinical data was collected during the course of infection including symptoms (upper respiratory, lower respiratory, systemic, and gastrointestinal symptoms). RNA was extracted from PBMCs collected at Day 0 in a subset of influenza infected patients (N=45) and was analyzed by RNA-Seq. Genes were ranked using Median Absolute Deviation (MAD) and then hierarchical clustering analysis was conducted using Spotfire and WGCNA. We detected two distinct clusters of individuals with large differences in their transcriptional landscapes falling into four clusters of genes. Principal components analysis was unable to define the clusters using any clinical traits including age, race, gender, and illness severity. One of the four clusters was characterized as an interferon response, where the other clusters have more complex annotations. Ongoing analyses are exploring upstream mechanisms that might lead to the observed divergent transcriptional outcomes.
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Zou, Min, Yves Barmaz, Melissa Preovolos, Leszek Popko, and Timothé Ménard. "Using Statistical Modeling for Enhanced and Flexible Pharmacovigilance Audit Risk Assessment and Planning." Therapeutic Innovation & Regulatory Science 55, no. 1 (August 17, 2020): 190–96. http://dx.doi.org/10.1007/s43441-020-00205-4.
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Abstract Background The European Medicines Agency Good Pharmacovigilance Practices (GVP) guidelines provide a framework for pharmacovigilance (PV) audits, including limited guidance on risk assessment methods. Quality assurance (QA) teams of large and medium sized pharmaceutical companies generally conduct annual risk assessments of the PV system, based on retrospective review of data and pre-defined impact factors to plan for PV audits which require a high volume of manual work and resources. In addition, for companies of this size, auditing the entire “universe” of individual entities on an annual basis is generally prohibitive due to sheer volume. A risk assessment approach that enables efficient, temporal, and targeted PV audits is not currently available. Methods In this project, we developed a statistical model to enable holistic and efficient risk assessment of certain aspects of the PV system. We used findings from a curated data set from Roche operational and quality assurance PV data, covering a span of over 8 years (2011–2019) and we modeled the risk with a logistic regression on quality PV risk indicators defined as data stream statistics over sliding windows. Results We produced a model for each PV impact factor (e.g. 'Compliance to Individual Case Safety Report') for which we had enough features. For PV impact factors where modeling was not feasible, we used descriptive statistics. All the outputs were consolidated and displayed in a QA dashboard built on Spotfire®. Conclusion The model has been deployed as a quality decisioning tool available to Roche Quality professionals. It is used, for example, to inform the decision on which affiliates (i.e. pharmaceutical company commercial entities) undergo audit for PV activities. The model will be continuously monitored and fine-tuned to ensure its reliability.
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Geyer, C. E., A. Martin, B. Newstat, M. A. Casey, M. S. Berger, C. R. Oliva, S. D. Rubin, S. Stein, and D. Cameron. "Lapatinib (L) plus capecitabine (C) in HER2+ advanced breast cancer (ABC): Genomic and updated efficacy data." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 1035. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.1035.
Повний текст джерелаАнотація:
1035 Background: EGF100151 demonstrated L+C improved TTP relative to C alone in women with HER2 positive, trastuzumab- exposed ABC (Geyer, NEJM;355(26):2006). We report updated efficacy data and results of correlative studies to determine if gene expression levels in the 5-FU and HER pathways are associated with clinical benefit in L+C. Methods: Tumor blocks are available on 217/399 patients, and so far sufficient mRNA has been extracted from 64/217 blocks using qRT-PCR. Tumors were evaluated for expression of HER1–4, TS, TP, PTEN, c-MYC. In addition to univariate and multivariate analyses, a SpotFire™ DecisionTree analysis was performed to determine the genes most significantly associated with RR; these genes were further analyzed for association with TTP. Results: Updated efficacy results through April 3, 2006 demonstrate: TTP L+C (27 wks)vs C (19 wks) HR 0.57 [0.43,0.77] p=0.00013; ORR L+C (24%)vs C (14%), Odds Ratio 1.9[1, 1.34] p=0.017; OS L+C vs C HR 0.78 [0.55,1.12] p=0.177; progression in CNS L+C (2%)vs C (11%) p=0.0445. Preliminary analysis of the first 64 samples indicates that elevated baseline mRNA expression of HER2 is associated with a higher RR and longer TTP (p<0.0001) with L+C. The opposite was seen in the C arm, where elevated HER2 mRNA expression seemed to predict for a poorer outcome. Analyses of ErbB3,4, PTEN and MYC as well as TS did not correlate with RR. Conclusion: The updated efficacy results confirm the prior demonstrated benefit of L+Cvs C and provide the first evidence for a systemic anti-HER2 therapy to have an effect on the development of CNS metastases. This preliminary analysis suggests a correlation between elevated HER2 mRNA levels and RR/TTP. Further investigation, including full genome microarray analysis of samples is ongoing. [Table: see text]
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Fabro, F., E. Tóth, L. J. M. Dekker, T. M. Luider, T. M. Pierson, and S. Leenstra. "P13.07 Multi-omics as a tool for elucidating temozolomide resistance in glioblastoma multiforme." Neuro-Oncology 21, Supplement_3 (August 2019): iii63. http://dx.doi.org/10.1093/neuonc/noz126.228.
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Abstract BACKGROUND Glioblastoma multiforme is the most common and aggressive brain tumor in adults, with an average overall survival of 14 months. Current standard of care consists of tumor resection followed by radiotherapy with concomitant temozolomide and adjuvant temozolomide. However, glioblastoma recurs in all patients. The causes reside in the enhanced invasiveness and resistance to treatment, giving a clear indication that recurrent and resistant glioblastoma biology must be understood better in order to achieve future treatment strategies to benefit the patients. The complex nature of recurrent glioblastoma makes its understanding still a challenging achievement in the field. Nowadays multi-omics approaching is developing further and further and it may be used to unravel, by combining different layers of biological information, a comprehensive view of the changes occurring during the treatment. MATERIAL AND METHODS A discovery set of 13 primary patient-derived glioblastoma stem-like cultures were analysed, comprising selected resistant, induced resistant and with pre-existing resistance conditions. A characterization of transcriptome, proteome and phosphoproteome was performed using RNAseq and liquid chromatography mass spectrometry. Additional 10 paired primary and recurrent tumor tissues were utilized as a validation set. The data obtained was visualised, explored and integrated through TIBCO Spotfire, Ingenuity Pathway Analysis, STRING and COREMINE medical software. RESULTS Genetic regulatory processes such as DNA repair mechanism, mRNA splicing and chromatin assembly were shown to be common over-represented trends in resistant and recurrent glioblastomas as a result of increased genomic instability and stress deriving from acute an repeated temozolomide exposure. Due to the immense heterogeneity of glioblastomas, other proteins and genes here identified as differentially expressed need a further investigation as they also may play an important role in relevant biological processes in a patient-specific way. CONCLUSION This study provides further understanding of glioblastoma biology revealing an association with processes of recurrence and temozolomide resistance, moreover offering potential therapeutic targets for better treatment options for glioblastoma patients.
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Alexander, V. J., R. P. Bissonnette, J. I. Rosen, T. Cooke, and F. M. Foss. "Retrospective analysis of cutaneous T-cell lymphoma (CTCL) biopsy samples for interleukin-2 receptor (IL2-R) subunit expression by immunohistochemistry (IHC) and real-time quantitative PCR (RT-PCR): Correlation to response to denileukin diftitox." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 20080. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.20080.
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20080 Background: Denileukin diftitox, a chimeric diphtheria toxin-IL2 protein, exerts its cytotoxic effect on cells expressing high or intermediate affinity IL2-R. IL2-R is a complex of 3 distinct polypeptide chains: IL2-Rα (CD25), IL2-Rβ (CD122), and IL2-Rγ (CD132). IL2-R α/β/γ heterotrimer binds with high affinity, IL2-R β/γ with intermediate affinity, and IL2-R α/γ with low affinity. Denileukin diftitox is indicated for patients with persistent or recurrent CTCL whose malignant cells express IL2-Rα protein. There is no currently available methodology to measure expression of the high affinity receptor in patient samples. This study was initiated to discover a correlation between expression of IL2-R components (at the mRNA and protein levels) and clinical response to denileukin diftitox. Methods: Of 33 available frozen clinical CTCL biopsy samples, 27 (10 responders) were sufficient for IHC. IL2-Rβ staining intensity was assigned a value of 0 (no staining relative to background), 1+ (weak), 2+ (moderate), or 3+ (strong). 22 samples (8 responders) were sufficient for RT-PCR. mRNA levels of the 3 IL2-R chains were normalized to 36B4 mRNA or 18S rRNA. Correlation between clinical response and IL2-R chain expression was assessed using Spotfire Decision Site. Results: The population of samples tested was representative of the study population. 26 of 27 samples exhibited 2+, all exhibited 1+, and none 3+ IL2-Rβ staining. The percentage of cells stained varied from 20%–90% for 1+ and 10%–80% for 2+ with no correlation to response. Correlation of levels of individual IL2-R subunit mRNA expression with response could not be established. Conclusions: Neither the IL2-Rβ IHC nor the RT-PCR assay, at current sensitivity levels, appear to identify denileukin diftitox responders. Larger sample datasets from current studies, and further assay refinement, are ongoing to define the merits of these approaches. [Table: see text]
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Uppal, Hirdesh, Kaushiki Mahapatra, Sock-Cheng Lewin-Koh, Steven Olsen, Mark X. Sliwkowski, Sandhya Girish, Dylan Hartley, Donna Dambach, and Vanitha Ramakrishnan. "Differential expression of microRNAs induced by trastuzumab emtansine (T-DM1) during megakaryocytopoiesis." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 645. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.645.
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645 Background: Treatment with the HER2-targeted antibody–drug conjugate T-DM1 resulted in significantly longer PFS and OS vs lapatinib + capecitabine in patients previously treated with trastuzumab and a taxane in the phase 3 study EMILIA. Thrombocytopenia (TCP) was the dose-limiting toxicity for patients treated with T-DM1, although platelets do not express HER2. In EMILIA, grade 3/4 TCP was observed in 12.9% of T-DM1-treated patients. We have previously shown that T-DM1 inhibits megakaryocyte (Mk) production and differentiation. Here, we investigated the effect of T-DM1 on microRNAs (miRNAs) associated with megakaryocytopoiesis. Methods: Human stem cells (HSCs; CD133+/CD34+) from 8 donors were differentiated into Mks in the presence of T-DM1, trastuzumab, or vehicle. Total RNA was extracted using the miRNeasy MiniKit. cDNA was prepared using the Taqman miRNA RT Kit, FAM-MGB probes, and stem-loop RT primer pool set. miRNA expression was measured using the 96.96 Dynamic Array Chip on the Biomark HD Reader. Data were analyzed using Fluidigm real-time analysis software Spotfire 5, and SAS 9.2. hsa−let−7g and hsa−miR−671−3p were chosen as reference miRNAs due to their low variation between treatments and time points. Median normalization was also applied. Results: A total of 526 miRNA RT-qPCR assays were used to map miRNA expression during differentiation of HSCs from 8 separate donors to Mks in vitro over 30 days. Several miRNAs demonstrated temporal changes in their expression profiles during maturation, suggesting these miRNAs are potential drivers of Mk differentiation. T-DM1 treatment inhibited Mk production and differentiation. Concomitant modifications in the expression of specific miRNAs were observed. These modifications were not present in trastuzumab- or vehicle-treated cells, suggesting these miRNAs may be involved in the development of T-DM1–induced TCP. Conclusions: These results suggest that the miRNAs have the potential to be used as biomarkers for TCP in patients treated with T-DM1 and possibly other DM1 conjugates. Specific miRNA alterations related to T-DM1 treatment will be discussed following investigations using clinical samples to validate these preliminary data.
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Gartrell, Robyn Denise, Douglas Kanter Marks, Thomas Hart, Edward Stack, Yan Lu, Camden Esancy, Camille Gerard, et al. "Characterizing the tumor microenvironment (TME) in primary melanomas using multiplex immunohistochemistry (mIHC)." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 9580. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.9580.
Повний текст джерелаАнотація:
9580 Background: Biomarkers are needed in primary melanoma to risk stratify for adjuvant trials. High levels of infiltrating cytotoxic (CD8+) T lymphocytes (CTLs) and low levels of CD68+ macrophages (MΦ) may correlate with prolonged survival but quantification methods are not standardized for clinical practice. HLA-DR is a marker of MΦ activation not expressed by suppressor myeloid cells. A novel pathology technique using mIHC allows for quantitative and spatial analysis of immune cell subsets. Methods: In a pilot set of stage II/III primary melanomas from Columbia University Medical Center (n = 94), clinical follow up is available for 51 cases. 32 had no evidence of recurrence at last follow up (minimum 2 years) while 19 died of melanoma. 5µm slides were stained using Opal multiplexed IHC (mIHC) for DAPI, CD3, CD8, CD68, SOX10, HLA-DR and Ki67. Tumor areas were pre-selected by a dermatopathologist, visualized using Mantra (Perkin Elmer) and analyzed using inForm (Perkin Elmer) and Spotfire (TIBCO). Results: In all patients (n = 94), CTLs are farther from tumor (SOX10+) cells when they are proliferating (Ki67+) (p < 0.0001***), while they are closer to MΦ when they are activated (HLA-DR+) (p = 0.0002***). Next, we evaluated impact on prognosis using disease specific survival (DSS) as an outcome based on median value (n = 51). In this exploratory study no correction for multiple comparisons was made. We find that CTL density correlates with prolonged DSS in tumor (p = 0.0185*) but not in stroma (p = 0.1630 ns). Ratio of density of CD8/CD68+HLA-DR- correlates with DSS in both tumor (p = 0.027*) and stroma (p = 0.017*). Finally, distance from CTLs to HLA-DR- MΦ was significantly greater in non-recurrent melanomas as compared to recurrent ones (p = 0.0167*). Conclusions: HLA-DR expression on MΦ and Ki67 expression on tumor cells correlate with position of CTLs in TME in primary melanoma. CTL density is a favorable prognostic marker while HLA-DR non-expressing MΦ may favor tumor progression. Quantitative mIHC allows for accurate spatial analysis of immune subsets within the TME and the development of novel, more accurate and potentially clinically relevant biomarkers.
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Baratti, Mariana O., Yuri B. Moreira, Fabiola Traina, Luciene Borges, Fernando F. Costa, Sergio Verjovski-Almeida, and Sara T. O. Saad. "Identification of Intronic RNA Expression in CD34+ Cells of Patients with Myelodysplatic Syndrome by RNA Microarray Analysis." Blood 110, no. 11 (November 16, 2007): 2423. http://dx.doi.org/10.1182/blood.v110.11.2423.2423.
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Abstract Myelodysplatic syndromes (MDS) are a group of clonal hematological disorders characterized by ineffective hematopoiesis with morphological evidence of marrow cell dysplasia resulting in peripheral blood cytopenia. Microarray technology has permitted a refined high-throughput mapping of the transcriptional activity in the human genome. RNAs transcribed from intronic regions of genes are involved in a number of processes related to post-transcriptional control of gene expression, and in the regulation of exon-skipping and intron retention. The characterization of intronic transcripts in progenitor cells of MDS patients could be an important strategic to understand the gene expression regulation in this disease. We conducted a pilot study in CD34+ cells of 4 MDS-RARS patients and 4 healthy individuals. Gene expression analysis was performed using a 44k intron-exon oligoarray custom-designed by Verjorvski-Almeida et al. and printed by Agilent Technologies. This oligoarray included protein-coding genes, sense and antisense strands of totally intronic noncoding (TIN) and partially intronic nonconding (PIN) RNAs. CD34+ cells were isolated from bone marrow samples using MACS magnetic columns. The quality of total extracted RNA was confirmed with the Agilent Bioanalyzer 2100. We amplified 300ng of each total RNA using the Agilent Low RNA Input Fluorescent Linear Amplification Kit PLUS, two-Color and samples were hybridized using the Gene Expression Hybridization Kit (Agilent) and then scanned on a GenePIX 4000B Scanner (Molecular Devices). The extraction analysis was performed using Agilent Feature Extration Software 9.5. Considering only the fluorescent spots in samples, the data were normalized by quantil using Spotfire DecisionSite®. To identify genes differentially expressed between MDS-RARS and healthy samples, we applied the SAM (Significance Analysis of microarray) approach using as parameters: two-class unpaired response, t-statistic, 1,000 permutations, fold > 2 and FDR = 0%. We identified 139 genes differentially expressed (67 up-regulated and 72 down-regulated), of which 33 were TIN and PIN transcripts (21 up-regulated and 12 down-regulated). These transcripts were grouped according to the main role: gene transcription (ZNF76, CC2D1A, ASXL1, TOP2B, NR4A3 and NR4A2); immune response (CTSH, CTSS, IFI30, NPY, SERPINA1 and PAG1); growth factor and receptor (RP5-1022P6.2, PRG4 and FGFR1OP2); adhesion (PPP1R15A and FN1); cell differentiation (B3GNT5, RALGPS1, C16orf67 and C5orf13); cell cycle and apoptosis (CYFIP2, PPP1R15A, DDX3X and NASP) and cellular trafficking (WIPI1, ICA1 and SLC11A2). These results demonstrated that 22% of all the genes differentially expressed correspond to TIN and PIN transcripts in CD34+ cells of MDS-RARS patients, suggesting that intronic transcripts can play an important role during the development of myelodysplastic syndrome.
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Gartrell, Robyn, Douglas Marks, Thomas Hart, Yan Lu, Ed Stack, Camden Esancy, Basil Horst, et al. "2367." Journal of Clinical and Translational Science 1, S1 (September 2017): 62–63. http://dx.doi.org/10.1017/cts.2017.224.
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OBJECTIVES/SPECIFIC AIMS: Precise biomarkers are urgently needed to characterize the tumor immune microenvironment in primary melanoma tumors both for prognostication and to predict the benefit of immuno-therapeutic intervention. The goal of this work is to define spatial relationships between CD8+ T cells, CD68+ macrophages and Sox10+ melanoma cells in order to define features correlating with prolonged survival METHODS/STUDY POPULATION: Five micrometer slides from either the primary biopsy or subsequent wide local excision procedure were stained using Opal multiplex IHC for DAPI, CD3 (LN10, Leica), CD8 (4B11, Leica), CD68 (KP1, Biogenex), SOX10 (BC34, Biocare), HLA-DR (LN-3, Abcam), and Ki67 (MIB1, Abcam). Cell phenotypes within representative fields preselected by a trained dermato-pathologist and were visualized using the Mantra quantitative pathology workstation (PerkinElmer), and analysis of spatial distribution of CD3+ CD8+ cells analyzed using inForm® image analysis software (PerkinElmer), and Spotfire software (TIBCO). In order to test whether mIHC can better characterize the tumor immune microenvironment, we screened databases at the Herbert Irving Cancer Center (HICC) at Columbia University for stage II/III melanoma patients diagnosed between 2000 and 2012, with available FFPE of primary melanoma tissue and documented clinical follow-up. We identified a preliminary population of 57 patients to begin our analysis. Clinical follow-up was available on 35 patients of whom 21 patients were alive with no evidence of recurrence or died with no evidence of recurrence and 14 had died of melanoma. Twenty-four patients had more than 24 months of survival information available but no detailed clinical information to determine cause of death. RESULTS/ANTICIPATED RESULTS: First, we evaluated whether density of immune cells in tumor and stroma predicted prognosis in 35 patients with disease specific survival information. We find that high number of CD3+CD8+ cells in tumor correlates with Disease Specific Survival (DSS) (p=0.0323*) and CD3+CD8+ cells in stroma may also correlate with DSS (p=0.0671). This is consistent with what is known in the literature regarding tumor infiltrating lymphocytes (TILs). We also found that CD68+ cells in stroma predict poor prognosis (0.0259*). This is consist with the proposed deleterious role for macrophages in tumor progression. Next, using nearest neighbor analysis we examined the effect of HLA-DR and Ki67 expression on spatial distribution of CD3+CD8+ T cells. We find that CD8+ T cells are closer to myeloid (CD68+) cells expressing HLA-DR. This is consistent with the potential of HLA-DR expressing cells to present antigens to T cells, and suggests that T cells may preferentially interact with HLA-DR expressing myeloid cells. Conversely, we find that Ki67 expression on tumor (SOX10+) cells correlates with increased distance from CD3+CD8+ T cells relative to SOX10+Ki67-tumor cells. This finding is consistent with the observation that more advanced tumors with higher mitotic rates have decreased T cell infiltrates, and suggests that dividing melanoma cells are less likely to interact with T cells. In addition, we performed analysis to determine whether spatial relationships defined above impact prognosis. Clinical oncology follow-up was available on 35 of the 57 patients evaluated above. We compared proximity of CD3+CD8+ cells to both myeloid (CD68+) and tumor (SOX10+) cells in patients who recurred and those with no evidence of recurrence. We found that CD3+CD8+ cells in patients who had recurrence were closer to CD68+ HLA-DR− cells than in patients who had no recurrence (t-test, p=0.0377), this correlated with DSS (p=0.003). Conversely, distance from CD3+CD8+ to CD68+ HLA-DR+ in relationship to recurrence was not significant with a trend towards CD3+CD8+ T cells being closer in nonrecurrent patients (t-test, p=0.1362). DISCUSSION/SIGNIFICANCE OF IMPACT: Consistent with the literature, we find that densities of CD8+ T cells correlates with favorable outcomes in early stage melanoma. We also find that density of CD68+ macrophages in stroma correlates with poor outcome. If proximity is a surrogate for interaction, these data indicate that dividing, Ki67+, melanoma cells interact less with CD8+ T cells than do Ki67+ melanoma cells. Further, HLA-DR expression on CD68+ infiltrating cells likely enhances their interaction with T cells. Interestingly, on further analysis, CD3+CD8+ cells were significantly closer to CD68+ HLA-DR− cells in patients who recurred, implying that interactions between these cell types may not be favorable. This analysis demonstrates that spatial analysis may be useful in predicting prognosis in early stage melanoma, and this is the first report of this type of analysis predicting outcomes in primary tumor specimens to our knowledge. Further staining and analysis of the complete patient cohort (n=120) is ongoing.
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Kaushal, Deepak, and Clayton W. Naeve. "Analyzing and Visualizing Expression Data with Spotfire." Current Protocols in Bioinformatics 7, no. 1 (September 2004). http://dx.doi.org/10.1002/0471250953.bi0709s7.
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Kaushal, Deepak, and Clayton W. Naeve. "An Overview of Spotfire for Gene‐Expression Studies." Current Protocols in Human Genetics 45, no. 1 (April 2005). http://dx.doi.org/10.1002/0471142905.hg1109s45.
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Kaushal, Deepak, and Clayton W. Naeve. "An Overview of Spotfire for Gene‐Expression Studies." Current Protocols in Bioinformatics 6, no. 1 (June 2004). http://dx.doi.org/10.1002/0471250953.bi0707s6.
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Kaushal, Deepak, and Clayton W. Naeve. "Loading and Preparing Data for Analysis in Spotfire." Current Protocols in Bioinformatics 6, no. 1 (June 2004). http://dx.doi.org/10.1002/0471250953.bi0708s6.
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Ky, Ashley, Jeffrey Bastar, Kristen Holmberg, Hana Bay, Tiffani Jones, Bethany Hearst, Thomas Davis, et al. "543. Perceived Ease of Use and Operator Performance of a rapid Multiplex PCR Diagnostic System in a Near Patient Setting." Open Forum Infectious Diseases 9, Supplement_2 (December 1, 2022). http://dx.doi.org/10.1093/ofid/ofac492.596.
Повний текст джерелаАнотація:
Abstract Background Access to multiplex molecular diagnostic tests for the rapid and accurate diagnosis of pharyngitis and other respiratory infections is limited in the near patient setting, but has potential to improve patient outcomes and antibiotic stewardship. The BioFire® Respiratory/Sore Throat (R/ST) Panel (bioMérieux, Salt Lake City, UT), designed for use with the BioFire® SpotFire System, is an Investigational Use Only (IUO) PCR-based sample-to-answer diagnostic test that identifies four bacteria and 10 viruses from nasopharyngeal swabs or throat swabs in ∼16 minutes. This study evaluated the ease of use and operator performance of the IUO R/ST Panel in the near patient setting. Methods A total of 35 test operators representative of the intended users in the near patient setting (i.e. non-laboratory professionals) participated across five study sites in the US and UK. Only Instrument and Panel Quick Guide training materials were provided during the eight months of R/ST Panel testing. Upon study completion, anonymous questionnaires were administered to assess operators’ perceived ease of use of the BioFire SpotFire System, R/ST Panel testing, and training materials; the accuracy of results interpretations were also evaluated. Further, results obtained by operators in the near patient setting and trained laboratory personnel were evaluated for reproducibility. Results Overall, 96.9% of operators reported that the system and panel were easy to use and that the provided training materials were sufficient to allow the user to perform the testing. The success rate of obtaining valid results on the initial test was 96.9%, similar to the rates observed for trained laboratory personnel. Reproducibility between site operators and trained laboratory personnel demonstrated an overall positive percent agreement of 99.0%. Conclusion The BioFire SpotFire System is an easy to use system that can be installed and operated in a near patient setting with minimal training. The R/ST Panel is also easy to use with minimal risk for user error. Implementation of this new system may aid in timely diagnosis and appropriate management of pharyngitis and other respiratory infections. Data presented are from assays that have not been cleared or approved for diagnostic use. Disclosures Ashley Ky, MLS(ASCP), bioMérieux: Employee|bioMérieux: Stocks/Bonds Jeffrey Bastar, PhD, bioMerieux: Employee|bioMerieux: Stocks/Bonds Kristen Holmberg, n/a, bioMerieux: Employee Hana Bay, BS, Biomerieux: Employee|Biomerieux: Stocks/Bonds Tiffani Jones, PhD, bioMerieux: Employee|bioMerieux: Stocks/Bonds Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support Virve Enne, BSc PhD, Biomerieux: Advisor/Consultant Cynthia Andjelic, PhD, bioMerieux: Employee.
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"C&EN Webinars - Mastering Medicinal Chemistry: Reinventing SAR through dynamic visual analytics in TIBCO Spotfire." Chemical & Engineering News Archive 91, no. 43 (October 28, 2013): 36. http://dx.doi.org/10.1021/cen-09143-ad15.
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Abzaltynova, Zhanna, and Janice Williams. "DEVELOPMENTS IN BUSINESS INTELLIGENCE SOFTWARE." Journal of Intelligence Studies in Business 3, no. 2 (August 28, 2013). http://dx.doi.org/10.37380/jisib.v3i2.68.
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In today’s economy the requirements in Business Intelligence environments are changing dramatically. This research paper tested underlying constructs. Hypothesis one sought to test if vendors seek to provide complete BI solutions following all four stages of the CI cycle. The evaluation of BI vendors indicates that all vendors examined do not support planning & directing phase, except for Astragy that gives users consultations to plan and arrange their CI, its absence did not influence the overall performance score. The second hypothesis sought to test if BI vendors fail to provide good enough solutions for the analysis part of the intelligence cycle. The research findings indicate that only two BI vendors, SAS and QlikView, delivering the analysis phase of the intelligence cycle in a proper way. The third hypothetical construct concerns BI vendors’ attempts at making considerable changes in software each year, with each new upgrade. By tracing and comparing the developments of the vendors selected it has been concluded that all BI vendors, irrespective of whether it is a leading traditional vendor or small innovative BI, follow the same tendency in introducing BI enhancements by striving to make its software cost-effective, simpler, faster and flexible for use, scalable to manage increasing amounts of data in businesses, accessible to employees at all levels of organization. Hypothesis four sought to find out if the BI vendors’ software tested can be divided into a number of meaningful subgroups. With reference to evaluation and analysis and empirical findings, it has been concluded that the BI vendors can be divided into sub groups and hence has been classified based on their support of the phases of the intelligence cycle, their developments and market information. The subgroups range from advanced, competent, partially competent, and inadequate to absolutely inadequate. Among the BI vendors assessed, none satisfied the criteria in the advanced category. Hypothesis five aspired to determine if the BI software evaluated should fall under a different term as some of them do not follow the entire BI cycle. The analysis of empirical findings identified that QlikView and TIBCO Spotfire deliver the so-called next generation in-memory analytics, which is faster, much simpler, more flexible and scalable and meet the present-day business needs to a far greater extent if compared to traditional BI.
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Bastar, Jeffrey, Ashley Ky, Kristen Holmberg, Hana Bay, Daria Drobysheva, Thomas Davis, Rangaraj Selvarangan, et al. "534. Evaluation of a Rapid Multiplex PCR Diagnostic Device for the Detection of Microorganisms from Nasopharyngeal and Throat Swab Specimens in the Near Patient Setting." Open Forum Infectious Diseases 9, Supplement_2 (December 1, 2022). http://dx.doi.org/10.1093/ofid/ofac492.587.
Повний текст джерелаАнотація:
Abstract Background Limited availability of multiplex molecular tests in the near-patient setting can impact the rapid diagnosis and treatment of patients experiencing symptoms of respiratory tract infections, including pharyngitis. The BioFire® Respiratory/Sore Throat (R/ST) Panel (bioMérieux, Salt Lake City, UT), designed for use with the BioFire® SpotFire System, is a PCR-based sample-to-answer diagnostic test that identifies four bacteria and 10 viruses (including SARS-CoV-2) from nasopharyngeal swab (NPS) or throat swab (TS) specimens in about 16 minutes. This study evaluated the performance of an Investigational Use Only (IUO) version of the BioFire R/ST Panel in the near patient setting. Methods NPS and TS specimens were prospectively enrolled from symptomatic consented/assented volunteers of all ages, or obtained as residual leftover specimens. Enrollment was conducted between December 2020 and September 2021 at five study sites in the US and UK (adult and pediatric emergency departments or urgent care clinics) with testing performed by personnel representative of the intended users (non-laboratory professionals). Several analytes that were not circulating during the COVID-19 pandemic were supplemented with archived specimens of known analyte composition. Performance was determined for both sample types by comparison to FDA cleared multiplex PCR tests or culture and PCR followed by sequencing of isolates (Streptococcus from throat swabs). Results A total of 1131 NPS and 452 TS prospectively collected specimens and 542 NPS and 128 TS archived specimens were tested with the BioFire R/ST Panel. For NPS specimens (prospective and archived) overall positive percent agreement (PPA) was 98.7% and negative percent agreement (NPA) was 99.1%, and for TS specimens (prospective and archived) overall PPA was 95.9% and NPA was 99.2%. Conclusion The BioFire R/ST Panel is a sensitive, specific, and robust test for rapid detection of a wide range of organisms in NPS and TS specimens in the near-patient setting. This test is expected to aid in the timely diagnosis and appropriate management of pharyngitis and other respiratory infections. Data presented are from assays that have not been cleared or approved for diagnostic use. Disclosures Jeffrey Bastar, PhD, MSCI, bioMerieux: Employee|bioMerieux: Stocks/Bonds Ashley Ky, MLS(ASCP), bioMérieux: Employee|bioMérieux: Stocks/Bonds Kristen Holmberg, n/a, bioMerieux: Employee Hana Bay, BS, Biomerieux: Employee|Biomerieux: Stocks/Bonds Daria Drobysheva, PhD, bioMerieux: Employee Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support Virve Enne, BSc PhD, Biomerieux: Advisor/Consultant Cynthia Andjelic, PhD, bioMerieux: Employee.