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Two-Step Mixed Model Approach to Analyzing Differential Alternative RNA Splicing
[article]
2020
bioRxiv
pre-print
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Kang H, Wilson CS, Harvey RC, Chen IM, Murphy MH, Atlas SR, et al. ...
doi:10.1101/2020.04.21.052886
fatcat:xfgvs247rndxrmjroevetoxurm
Ovarian Tumor Microenvironment Signaling: Convergence on the Rac1 GTPase
2018
Cancers
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The tumor microenvironment for epithelial ovarian cancer is complex and rich in bioactive molecules that modulate cell-cell interactions and stimulate numerous signal transduction cascades. These signals ultimately modulate all aspects of tumor behavior including progression, metastasis and therapeutic response. Many of the signaling pathways converge on the small GTPase Ras-related C3 botulinum toxin substrate (Rac)1. In addition to regulating actin cytoskeleton remodeling necessary for tumor
doi:10.3390/cancers10100358
pmid:30261690
pmcid:PMC6211091
fatcat:rixfhktnkvc55flasjuv6hsg2e
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... ell adhesion, migration and invasion, Rac1 through its downstream effectors, regulates cancer cell survival, tumor angiogenesis, phenotypic plasticity, quiescence, and resistance to therapeutics. In this review we discuss evidence for Rac1 activation within the ovarian tumor microenvironment, mechanisms of Rac1 dysregulation as they apply to ovarian cancer, and the potential benefits of targeting aberrant Rac1 activity in this disease. The potential for Rac1 contribution to extraperitoneal dissemination of ovarian cancer is addressed.
Efficiently estimating small p-values in permutation tests using importance sampling and cross-entropy method
[article]
2016
arXiv
pre-print
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Permutation tests are commonly used for estimating p-values from statistical hypothesis testing when the sampling distribution of the test statistic under the null hypothesis is not available or unreliable for finite sample sizes. One critical challenge for permutation tests in genomic studies is that an enormous number of permutations is needed for obtaining reliable estimations of small p-values, which requires intensive computational efforts. In this paper, we develop a computationally
arXiv:1608.00053v1
fatcat:7j3e72vfrbda5fijm75m4lnvvm
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... ent algorithm for evaluating small p-values from permutation tests based on an adaptive importance sampling approach, which uses the cross-entropy method for finding the optimal proposal density. Simulation studies and analysis of a real microarray dataset demonstrate that our approach achieves considerable gains in computational efficiency comparing with existing methods.
Pediatric B-lymphoblastic leukemia with RUNX1 amplification: clinicopathologic study of eight cases
2011
Modern Pathology
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B-lymphoblastic leukemia (a.k.a. precursor B-cell acute lymphoblastic leukemia) is a heterogeneous disease at the clinical, morphologic, immunophenotypic and genetic levels. Recurrent genetic abnormalities in B-lymphoblastic leukemia with prognostic significance are well known and specifically delineated in the WHO 2008 classification (eg hyperdiploidy, t(9;22)(q34;q11.2); BCR-ABL1, t(12;21)(p13;q22); ETV6-RUNX1). In recent years, a subgroup of B-lymphoblastic leukemia with the recurring
doi:10.1038/modpathol.2011.118
pmid:21822204
fatcat:e47fa5cnhrdonb4hgyvisvj4vm
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... alteration of RUNX1 amplification has emerged. This subgroup has a low incidence (2%) and an increased risk of relapse and overall worse outcome. Given these apparently distinctive clinicopathologic features, we evaluated eight cases of pediatric B-lymphoblastic leukemia with RUNX1 amplification treated on Children's Oncology Group protocols from 2000-2009. Compared with 25 consecutive B-lymphoblastic leukemia cases without RUNX1 amplification, we identified a trend toward male predominance (P-value ¼ 0.082) and low white blood cell count at presentation (P-value ¼ 0.081) in B-lymphoblastic leukemia with RUNX1 amplification. Older age at presentation was significant (median age 9.5 years, P-value ¼ 0.006). There was no significant difference in the presence of central nervous system disease, CD20 or myeloid antigen positivity on the blasts or percent circulating blasts in B-lymphoblastic leukemia with RUNX1 amplification versus other B-lymphoblastic leukemia types. Seven of eight patients (88%) are alive and free of disease at the time of last checkup (mean 50 months, range 14-116 months). Although we see a relatively good outcome in our small cohort of patients, recent findings from the Children's Oncology Group on a large set of patients suggests otherwise that these patients may have an inferior outcome compared with patients with B-lymphoblastic leukemia without RUNX1 amplification. Longterm follow-up in larger cohorts including minimal residual disease correlation is required.
Study on Hot Deformation Behavior of High Strength Construction Steel 34CrNiMo6
2018
MATEC Web of Conferences
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The hot pressure deformation tests were carried out by using Gleeble-2000 simulator at the temperature of 950 ℃ ~ 1150 ℃ and strain rate of 0.001s -1 ~ 1s -1 for a kind of high strength construction steel 34CrNiMo6 for Crankshafts and the curve of its flow stress were obtained. By studied the data, the flow stress constitutive equation, hot deforming active energy and the Z parameter were obtained. The curve of flow stress of 34CrNiMo6 steel indicated that the flow stress was increased with the
doi:10.1051/matecconf/201714202009
fatcat:45ulziplvjaqzfhyhwjswspm3m
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... decrease of temperature or increase of the strain rate. During the deformation, temperature and strain rate take important effect on dynamic recrystallization and dynamic recovery. It was propitious to dynamic recrystallization with raising temperature or reducing strain rate, and also made for the refinement of grain.
Study on Hot Deformation Behavior of High Strength Construction Steel 34CrNiMo6
2018
MATEC Web of Conferences
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The hot pressure deformation tests were carried out by using Gleeble-2000 simulator at the temperature of 950 ℃ ~ 1150 ℃ and strain rate of 0.001s -1 ~ 1s -1 for a kind of high strength construction steel 34CrNiMo6 for Crankshafts and the curve of its flow stress were obtained. By studied the data, the flow stress constitutive equation, hot deforming active energy and the Z parameter were obtained. The curve of flow stress of 34CrNiMo6 steel indicated that the flow stress was increased with the
doi:10.1051/matecconf/201814202009
fatcat:nmowwmvoszeplmjdeitg32kyle
more »
... decrease of temperature or increase of the strain rate. During the deformation, temperature and strain rate take important effect on dynamic recrystallization and dynamic recovery. It was propitious to dynamic recrystallization with raising temperature or reducing strain rate, and also made for the refinement of grain.
Preparation and Performance of Gallium Nitride Powders with Preferred Orientation
2018
MATEC Web of Conferences
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The paper prepared the III-V semiconductor, hexagonal wurtzite Gallium nitride powders by calcining a gallium oxide in flowing ammonia above 900°C (1173K). Because of the solid-state reaction process that the gallium oxide transformed to GaN through solid-state gallium oxynitrides (GaOxNy) as inter-mediates, the Gallium nitride powders which are agglomerates of tens nanometers flake crystallites retain the rod shape and grain size of raw gallium oxide and have slight (002) plane preferred
doi:10.1051/matecconf/201814201009
fatcat:ra52ftylxndifjogdhe4ox5grq
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... ation. The near-edge emission of Gallium nitride at 346 nm has a blue shift of 187 meV attributed to a decrease in disorder of the material that is decided by the (002) plane preferred orientation. The preferred orientation and a blue shift have some kind of reference significance to single crystal growth.
Preparation and Performance of Gallium Nitride Powders with Preferred Orientation
2018
MATEC Web of Conferences
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The paper prepared the III-V semiconductor, hexagonal wurtzite Gallium nitride powders by calcining a gallium oxide in flowing ammonia above 900°C (1173K). Because of the solid-state reaction process that the gallium oxide transformed to GaN through solid-state gallium oxynitrides (GaOxNy) as inter-mediates, the Gallium nitride powders which are agglomerates of tens nanometers flake crystallites retain the rod shape and grain size of raw gallium oxide and have slight (002) plane preferred
doi:10.1051/matecconf/201714201009
fatcat:sdao7wgssndi5j52d3f2hqm32m
more »
... ation. The near-edge emission of Gallium nitride at 346 nm has a blue shift of 187 meV attributed to a decrease in disorder of the material that is decided by the (002) plane preferred orientation. The preferred orientation and a blue shift have some kind of reference significance to single crystal growth.
Two-step mixed model approach to analyzing differential alternative RNA splicing
2020
PLoS ONE
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Methodology: Li Luo, Huining Kang, Christine A. Stidley. Software: Li Luo, Huining Kang. Visualization: Li Luo, Huining Kang, Christine A. Stidley. ...
(PDF) Conceptualization: Li Luo, Huining Kang, Scott A. Ness, Christine A. Stidley. Data curation: Li Luo, Huining Kang, Xichen Li. ...
doi:10.1371/journal.pone.0232646
pmid:33035235
fatcat:i24ohdlonngitkgx2gchfgpzfi
Global Autozygosity Is Associated with Cancer Risk, Mutational Signature and Prognosis
2020
Cancers
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Global autozygosity quantifies the genome-wide levels of homozygous and heterozygous variants. It is the signature of non-random reproduction, though it can also be driven by other factors, and has been used to assess risk in various diseases. However, the association between global autozygosity and cancer risk has not been studied. From 4057 cancer subjects and 1668 healthy controls, we found strong associations between global autozygosity and risk in ten different cancer types. For example,
doi:10.3390/cancers12123646
pmid:33291726
fatcat:bl7xi7jueran3a7i2jq5zthsqe
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... e heterozygosity ratio was found to be significantly associated with breast invasive carcinoma in Blacks and with male skin cutaneous melanoma in Caucasians. We also discovered eleven associations between global autozygosity and mutational signatures which can explain a portion of the etiology. Furthermore, four significant associations for heterozygosity ratio were revealed in disease-specific survival analyses. This study demonstrates that global autozygosity is effective for cancer risk assessment.
A Two-Part Mixed Model for Differential Expression Analysis in Single-Cell High-Throughput Gene Expression Data
2022
Genes
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The high-throughput gene expression data generated from recent single-cell RNA sequencing (scRNA-seq) and parallel single-cell reverse transcription quantitative real-time PCR (scRT-qPCR) technologies enable biologists to study the function of transcriptome at the level of individual cells. Compared with bulk RNA-seq and RT-qPCR gene expression data, single-cell data show notable distinct features, including excessive zero expression values, high variability, and clustered design. We propose to
doi:10.3390/genes13020377
pmid:35205420
pmcid:PMC8872627
fatcat:7yiuyarprbavrkfypa5xt3vn3m
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... model single-cell high-throughput gene expression data using a two-part mixed model, which not only adequately accounts for the aforementioned features of single-cell expression data but also provides the flexibility of adjusting for covariates. An efficient computational algorithm, automatic differentiation, is used for estimating the model parameters. Compared with existing methods, our approach shows improved power for detecting differential expressed genes in single-cell high-throughput gene expression data.
Dysregulated transcriptional networks in KMT2A- and MLLT10-rearranged T-ALL
2018
Biomarker Research
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For children and young adults with T-lineage acute lymphoblastic leukemia (T-ALL), event free survival following relapse is < 10%. We recently showed that rearrangements of the mixed lineage leukemia gene (KMT2A-R) are associated with induction failure and an inferior survival in T-ALL. Because there are currently no molecular features that inform treatment strategies in T-ALL, we hypothesized that transcriptional alterations related to KMT2A-R and MLLT10-R T-ALL could identify biologically
doi:10.1186/s40364-018-0141-z
pmid:30159143
fatcat:r2t5lp7xn5hz7co54xiyzm2acu
more »
... vant genes and signaling pathways for the development of targeted therapies for these groups of patients. We analyzed microarray data from a retrospective cohort of 100 T-ALL patients to identify novel targets for KMT2A (n = 12) or MLLT10 (n = 9) chimeras. We identified 330 probe sets that could discriminate between these groups, including novel targets, like RUNX2, TCF4 or MYO6. The results were further validated in two independent data sets and the functional networks were analyzed to identify pathways that may be of pathogenic or therapeutic relevance.
High Incidence of ErbB3, ErbB4, and MET Expression in Ovarian Cancer
2014
International Journal of Gynecological Pathology
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MetaGSCA: A tool for meta-analysis of gene set differential coexpression
2021
PLoS Computational Biology
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Analyses of gene set differential coexpression may shed light on molecular mechanisms underlying phenotypes and diseases. However, differential coexpression analyses of conceptually similar individual studies are often inconsistent and underpowered to provide definitive results. Researchers can greatly benefit from an open-source application facilitating the aggregation of evidence of differential coexpression across studies and the estimation of more robust common effects. We developed Meta
doi:10.1371/journal.pcbi.1008976
pmid:33945541
pmcid:PMC8121311
fatcat:bmo6uhzbxbghbfi4pqurzzly7a
more »
... e Set Coexpression Analysis (MetaGSCA), an analytical tool to systematically assess differential coexpression of an a priori defined gene set by aggregating evidence across studies to provide a definitive result. In the kernel, a nonparametric approach that accounts for the gene-gene correlation structure is used to test whether the gene set is differentially coexpressed between two comparative conditions, from which a permutation test p-statistic is computed for each individual study. A meta-analysis is then performed to combine individual study results with one of two options: a random-intercept logistic regression model or the inverse variance method. We demonstrated MetaGSCA in case studies investigating two human diseases and identified pathways highly relevant to each disease across studies. We further applied MetaGSCA in a pan-cancer analysis with hundreds of major cellular pathways in 11 cancer types. The results indicated that a majority of the pathways identified were dysregulated in the pan-cancer scenario, many of which have been previously reported in the cancer literature. Our analysis with randomly generated gene sets showed excellent specificity, indicating that the significant pathways/gene sets identified by MetaGSCA are unlikely false positives. MetaGSCA is a user-friendly tool implemented in both forms of a Web-based application and an R package "MetaGSCA". It enables comprehensive meta-analyses of gene set differential coexpression data, with an optional module of post hoc pathway crosstalk network analysis to identify and visualize pathways having similar coexpression profiles.
Efficient Transmission and Propagation of Tomato Chlorosis Virus by Simple Single-Leaflet Grafting
2017
The Plant Pathology Journal
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Tomato chlorosis virus (ToCV), a member of the genus Crinivirus, has caused an epidemic disease in tomato worldwide. ToCV is phloem-limited and transmitted by whiteflies in a semi-persistent manner, but not by mechanical inoculation. Experimental propagation of ToCV has been performed primarily by using whitefly-mediated inoculation. To develop a simple and convenient method for transmission of ToCV, we investigated grafting single-leaflets from tomato plants infected with ToCV to recipient
doi:10.5423/ppj.nt.02.2017.0039
pmid:28592953
pmcid:PMC5461053
fatcat:fuhfruqes5bfhou7ux3dlxmpqa
more »
... to seedlings. Forty-one of 46 tomato seedlings tested were grafted successfully with single-leaflets infected with ToCV. Among them, 36 seedlings (87.8%) were systemically infected with ToCV and developed typical symptoms. Our results demonstrated that single-leaflet grafting could provide a sufficient amount of inoculum for the transmission of ToCV to the grafted seedlings.
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