139,550 research outputs found
Identification of dfferentially expressed genes and false discovery rate in microarray studies
No full textRevie
Joint estimation of isoform expression and isoform-specific read distribution using multisample RNA-Seq data.
No full textMOTIVATION:
RNA-sequencing technologies provide a powerful tool for expression analysis at gene and isoform level, but accurate estimation of isoform abundance is still a challenge. Standard assumption of uniform read intensity would yield biased estimates when the read intensity is in fact non-uniform. The problem is that, without strong assumptions, the read intensity pattern is not identifiable from data observed in a single sample.
RESULTS:
We develop a joint statistical model that accounts for non-uniform isoform-specific read distribution and gene isoform expression estimation. The main challenge is in dealing with the large number of isoform-specific read distributions, which potentially are as many as the number of splice variants in the genome. A statistical regularization via a smoothing penalty is imposed to control the estimation. Also, for identifiability reasons, the method uses information across samples from the same region. We develop a fast and robust computational procedure based on the iterated-weighted least-squares algorithm, and apply it to simulated data and two real RNA-Seq datasets with reverse transcription-polymerase chain reaction validation. Empirical tests show that our model performs better than existing methods in terms of increasing precision in isoform-level estimation.
AVAILABILITY AND IMPLEMENTATION:
We have implemented our method in an R package called Sequgio as a pipeline for fast processing of RNA-Seq data
Multidimensional local false discovery rate for microarray studies
No full textMotivation: The false discovery rate (fdr) is a key tool for statistical
assessment of differential expression (DE) in microarray studies.
Overall control of the fdr alone, however, is not sufficient to address
the problem of genes with small variance, which generally suffer
from a disproportionally high rate of false positives. It is desirable to
have an fdr-controlling procedure that automatically accounts for gene
variability.
Methods: We generalize the local fdr as a function of multiple statistics,
combining a common test statistic for assessing DE with its standard
error information. We use a non-parametric mixture model for DE and
non-DE genes to describe the observed multi-dimensional statistics,
and estimate the distribution for non-DE genes via the permutation
method. We demonstrate this fdr2d approach for simulated and real
microarray data.
Results: The fdr2d allows objective assessment of DE as a function
of gene variability. We also show that the fdr2d performs better than
commonly used modified test statistics.
Availability: An R-package OCplus containing functions for comput-
ing fdr2d( ) and other operating characteristics of microarray data is
available at http://www.meb.ki.se/~yudpa
Tobacco use, body mass index and the risk of malignant lymphomas - A nationwide cohort study in Sweden
No full textIn the search for risk factors involved in the etiology of lymphoproliferative malignancies there is still inconsistent evidence regarding effects of smoking tobacco, and the role of smokeless tobacco is poorly investigated. New evidence indicates that excess body weight increases the risk of NHL and HD. To determine if tobacco use of various forms and high Body Mass Index (BMI) affect the occurrence of these neoplasms, we conducted a prospective cohort study on over 330,000 Swedish construction workers included in the Construction Industry Working Environment and Health program. Information on smoking, snuff dipping, height and weight was gathered by self administered questionnaires together with personal interviews. Cancer incidence was ascertained through the year 2000 by record linkage to the nationwide Swedish Cancer Registry, Migration Registry and Cause of Death Registry. At the end of follow up, 1,309 subjects had been diagnosed with NHL (including chronic lymphocytic leukemia) and 205 with HD respectively. Age adjusted incidence rate ratios were computed using Cox proportional Hazard regression modeling. Smoking cigarette, pipe or cigar was not associated with NHL or HD. There was no evidence indicating a relation between quantity and duration of smoking and NHL or HD risk. No link was found between NHL and usage of smokeless tobacco. Having a BMI of 30 or higher did not convey excess risk of developing NHL or HD compared to normal weight (BMI 18.6-24.9). We conclude that tobacco smoking and high BMI do not entail an increased risk of NHL and HD. Our findings of a relation between the duration of snuff dipping and HD need further investigation. © 2005 Wiley-Liss, Inc
CREDO: Highly confident disease-relevant A-to-I RNA-editing discovery in breast cancer
No full textAdenosine-to-Inosine (A-to-I) RNA editing is the most prevalent post-transcriptional modification of RNA molecules. Researchers have attempted to find reliable RNA editing using next generation sequencing (NGS) data. However, most of these attempts suffered from a high rate of false positives, and they did not consider the clinical relevance of the identified RNA editing, for example, in disease progression. We devised an effective RNA-editing discovery pipeline called CREDO, which includes novel statistical filtering modules based on integration of DNA- and RNA-seq data from matched tumor-normal tissues. CREDO was compared with three other RNA-editing discovery pipelines and found to give significantly fewer false positives. Application of CREDO to breast cancer data from the Cancer Genome Atlas (TCGA) project discovered highly confident RNA editing with clinical relevance to cancer progression in terms of patient survival. RNA-editing detection using DNA- and RNA-seq data from matched tumor-normal tissues should be more routinely performed as multiple omics data are becoming commonly available from each patient sample. We believe CREDO is an effective and reliable tool for this problem
Tobacco use, body mass index, and the risk of leukemia and multiple myeloma: A nationwide cohort study in Sweden
No full textIn a prospective cohort study of more than 330,000 Swedish construction workers, we explored the effect of tobacco smoking, oral moist snuff use, and body mass index (BMI) on the risk of developing leukemia (excluding chronic lymphocytic leukemia) and multiple myeloma (MM). Study subjects were participants of a health surveillance system within the building industry. Record linkage to the nationwide Swedish cancer registry, migration registry, and cause of death registry made a comprehensive follow-up available. A total of 372 incident cases of leukemia and 520 subjects with MM was ascertained. An increase in risk of acute myelogenous leukemia (AML) was observed in current smokers (incidence rate ratio, 1.50; 95% confidence interval, 1.06-2.11). Furthermore, there was an indication of a possible association between smoking intensity and risk of acute lymphocytic leukemia. Results on snuff use as well as BMI showed no association. This study confirms the role of smoking as a risk factor for AML and gives no support to the hypothesis of a role of snuff use or BMI level on the risk of leukemia or MM. ©2007 American Association for Cancer Research
Identification of recurrent regions of copy-number variants across multiple individuals
No full text10.1186/1471-2105-11-147BMC Bioinformatics1
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