اشترك بالحزمة الذهبية واحصل على وصول غير محدود شمرا أكاديميا
تسجيل مستخدم جديدSASeq: A Selective and Adaptive Shrinkage Approach to Detect and Quantify Active Transcripts using RNA-Seq
149
0
0.0
(
0
)
اسأل ChatGPT حول البحث
ﻻ يوجد ملخص باللغة العربية
Identification and quantification of condition-specific transcripts using RNA-Seq is vital in transcriptomics research. While initial efforts using mathematical or statistical modeling of read counts or per-base exonic signal have been successful, they may suffer from model overfitting since not all the reference transcripts in a database are expressed under a specific biological condition. Standard shrinkage approaches, such as Lasso, shrink all the transcript abundances to zero in a non-discriminative manner. Thus it does not necessarily yield the set of condition-specific transcripts. Informed shrinkage approaches, using the observed exonic coverage signal, are thus desirable. Motivated by ubiquitous uncovered exonic regions in RNA-Seq data, termed as naked exons, we propose a new computational approach that first filters out the reference transcripts not supported by splicing and paired-end reads, then followed by fitting a new mathematical model of per-base exonic coverage signal and the underlying transcripts structure. We introduce a tuning parameter to penalize the specific regions of the selected transcripts that were not supported by the naked exons. Our approach compares favorably with the selected competing methods in terms of both time complexity and accuracy using simulated and real-world data. Our method is implemented in SAMMate, a GUI software suite freely available from http://sammate.sourceforge.net
قيم البحث
اقرأ أيضاً
RNA-seq has rapidly become the de facto technique to measure gene expression. However, the time required for analysis has not kept up with the pace of data generation. Here we introduce Sailfish, a novel computational method for quantifying the abund
ance of previously annotated RNA isoforms from RNA-seq data. Sailfish entirely avoids mapping reads, which is a time-consuming step in all current methods. Sailfish provides quantification estimates much faster than existing approaches (typically 20-times faster) without loss of accuracy.
RNA-Seq technology allows for studying the transcriptional state of the cell at an unprecedented level of detail. Beyond quantification of whole-gene expression, it is now possible to disentangle the abundance of individual alternatively spliced tran
script isoforms of a gene. A central question is to understand the regulatory processes that lead to differences in relative abundance variation due to external and genetic factors. Here, we present a mixed model approach that allows for (i) joint analysis and genetic mapping of multiple transcript isoforms and (ii) mapping of isoform-specific effects. Central to our approach is to comprehensively model the causes of variation and correlation between transcript isoforms, including the genomic background and technical quantification uncertainty. As a result, our method allows to accurately test for shared as well as transcript-specific genetic regulation of transcript isoforms and achieves substantially improved calibration of these statistical tests. Experiments on genotype and RNA-Seq data from 126 human HapMap individuals demonstrate that our model can help to obtain a more fine-grained picture of the genetic basis of gene expression variation.
The analysis of differential gene expression from RNA-Seq data has become a standard for several research areas mainly involving bioinformatics. The steps for the computational analysis of these data include many data types and file formats, and a wi
de variety of computational tools that can be applied alone or together as pipelines. This paper presents a review of differential expression analysis pipeline, addressing its steps and the respective objectives, the principal methods available in each step and their properties, bringing an overview in an organized way in this context. In particular, this review aims to address mainly the aspects involved in the differentially expressed gene (DEG) analysis from RNA sequencing data (RNA-Seq), considering the computational methods and its properties. In addition, a timeline of the evolution of computational methods for DEG is presented and discussed, as well as the relationships existing between the main computational tools are presented by an interaction network. A discussion on the challenges and gaps in DEG analysis is also highlighted in this review.
Background: Since the invention of next-generation RNA sequencing (RNA-seq) technologies, they have become a powerful tool to study the presence and quantity of RNA molecules in biological samples and have revolutionized transcriptomic studies. The a
nalysis of RNA-seq data at four different levels (samples, genes, transcripts, and exons) involve multiple statistical and computational questions, some of which remain challenging up to date. Results: We review RNA-seq analysis tools at the sample, gene, transcript, and exon levels from a statistical perspective. We also highlight the biological and statistical questions of most practical considerations. Conclusion: The development of statistical and computational methods for analyzing RNA- seq data has made significant advances in the past decade. However, methods developed to answer the same biological question often rely on diverse statical models and exhibit different performance under different scenarios. This review discusses and compares multiple commonly used statistical models regarding their assumptions, in the hope of helping users select appropriate methods as needed, as well as assisting developers for future method development.
Radiomic models have been shown to outperform clinical data for outcome prediction in glioblastoma (GBM). However, clinical implementation is limited by lack of parameters standardization. We aimed to compare nine machine learning classifiers, with d
ifferent optimization parameters, to predict overall survival (OS), isocitrate dehydrogenase (IDH) mutation, O-6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation, epidermal growth factor receptor (EGFR) VII amplification and Ki-67 expression in GBM patients, based on radiomic features from conventional and advanced MR. 156 adult patients with pathologic diagnosis of GBM were included. Three tumoral regions were analyzed: contrast-enhancing tumor, necrosis and non-enhancing tumor, selected by manual segmentation. Radiomic features were extracted with a custom version of Pyradiomics, and selected through Boruta algorithm. A Grid Search algorithm was applied when computing 4 times K-fold cross validation (K=10) to get the highest mean and lowest spread of accuracy. Once optimal parameters were identified, model performances were assessed in terms of Area Under The Curve-Receiver Operating Characteristics (AUC-ROC). Metaheuristic and ensemble classifiers showed the best performance across tasks. xGB obtained maximum accuracy for OS (74.5%), AB for IDH mutation (88%), MGMT methylation (71,7%), Ki-67 expression (86,6%), and EGFR amplification (81,6%). Best performing features shed light on possible correlations between MR and tumor histology.
سجل دخول لتتمكن من نشر تعليقات
التعليقات
جاري جلب التعليقات
سجل دخول لتتمكن من متابعة معايير البحث التي قمت باختيارها
