Quantitative model for inferring dynamic regulation of the tumour suppressor gene p53

Background  

The availability of various "omics" datasets creates a prospect of performing the study of genome-wide genetic regulatory networks. However, one of the major challenges of using mathematical models to infer genetic regulation from microarray datasets is the lack of information for protein concentrations and activities. Most of the previous researches were based on an assumption that the mRNA levels of a gene are consistent with its protein activities, though it is not always the case. Therefore, a more sophisticated modelling framework together with the corresponding inference methods is needed to accurately estimate genetic regulation from "omics" datasets.     

Preferred analysis methods for Affymetrix GeneChips. II. An expanded,balanced, wholly-defined spike-in dataset

Background  

Concomitant with the rise in the popularity of DNA microarrays has been a surge of proposed methods for the analysis of microarray data. Fully controlled "spike-in" datasets are an invaluable but rare tool for assessing the performance of various methods.     

Clustering gene expression data with a penalized graph-based metric

Background  

The search for cluster structure in microarray datasets is a base problem for the so-called "-omic sciences". A difficult problem in clustering is how to handle data with a manifold structure, i.e. data that is not shaped in the form of compact clouds of points, forming arbitrary shapes or paths embedded in a high-dimensional space, as could be the case of some gene expression datasets.     

Protein interaction network topology uncovers melanogenesis regulatory network components within functional genomics datasets

Background  

RNA-mediated interference (RNAi)-based functional genomics is a systems-level approach to identify novel genes that control biological phenotypes. Existing computational approaches can identify individual genes from RNAi datasets that regulate a given biological process. However, currently available methods cannot identify which RNAi screen "hits" are novel components of well-characterized biological pathways known to regulate the interrogated phenotype. In this study, we describe a method to identify genes from RNAi datasets that are novel components of known biological pathways. We experimentally validate our approach in the context of a recently completed RNAi screen to identify novel regulators of melanogenesis.     

Comparative evaluation of gene-set analysis methods

Background  

Multiple data-analytic methods have been proposed for evaluating gene-expression levels in specific biological pathways, assessing differential expression associated with a binary phenotype. Following Goeman and Bühlmann's recent review, we compared statistical performance of three methods, namely Global Test, ANCOVA Global Test, and SAM-GS, that test "self-contained null hypotheses" Via. subject sampling. The three methods were compared based on a simulation experiment and analyses of three real-world microarray datasets.     

A benchmark for statistical microarray data analysis that preserves actual biological and technical variance

Background  

Recent reanalysis of spike-in datasets underscored the need for new and more accurate benchmark datasets for statistical microarray analysis. We present here a fresh method using biologically-relevant data to evaluate the performance of statistical methods.     

Reconstructing phylogenies from noisy quartets in polynomial time with a high success probability

Background  

In recent years, quartet-based phylogeny reconstruction methods have received considerable attentions in the computational biology community. Traditionally, the accuracy of a phylogeny reconstruction method is measured by simulations on synthetic datasets with known "true" phylogenies, while little theoretical analysis has been done. In this paper, we present a new model-based approach to measuring the accuracy of a quartet-based phylogeny reconstruction method. Under this model, we propose three efficient algorithms to reconstruct the "true" phylogeny with a high success probability.     

MASPECTRAS: a platform for management and analysis of proteomics LC-MS/MS data

Background  

The advancements of proteomics technologies have led to a rapid increase in the number, size and rate at which datasets are generated. Managing and extracting valuable information from such datasets requires the use of data management platforms and computational approaches.     

Discover protein sequence signatures from protein-protein interaction data

Background  

The development of high-throughput technologies such as yeast two-hybrid systems and mass spectrometry technologies has made it possible to generate large protein-protein interaction (PPI) datasets. Mining these datasets for underlying biological knowledge has, however, remained a challenge.     

Missing value imputation for microarray gene expression data using histone acetylation information

Background  

It is an important pre-processing step to accurately estimate missing values in microarray data, because complete datasets are required in numerous expression profile analysis in bioinformatics. Although several methods have been suggested, their performances are not satisfactory for datasets with high missing percentages.     

Network-based logistic regression integration method for biomarker identification

Background

Many mathematical and statistical models and algorithms have been proposed to do biomarker identification in recent years. However, the biomarkers inferred from different datasets suffer a lack of reproducibilities due to the heterogeneity of the data generated from different platforms or laboratories. This motivates us to develop robust biomarker identification methods by integrating multiple datasets.

Methods

In this paper, we developed an integrative method for classification based on logistic regression. Different constant terms are set in the logistic regression model to measure the heterogeneity of the samples. By minimizing the differences of the constant terms within the same dataset, both the homogeneity within the same dataset and the heterogeneity in multiple datasets can be kept. The model is formulated as an optimization problem with a network penalty measuring the differences of the constant terms. The L₁ penalty, elastic penalty and network related penalties are added to the objective function for the biomarker discovery purpose. Algorithms based on proximal Newton method are proposed to solve the optimization problem.

Results

We first applied the proposed method to the simulated datasets. Both the AUC of the prediction and the biomarker identification accuracy are improved. We then applied the method to two breast cancer gene expression datasets. By integrating both datasets, the prediction AUC is improved over directly merging the datasets and MetaLasso. And it’s comparable to the best AUC when doing biomarker identification in an individual dataset. The identified biomarkers using network related penalty for variables were further analyzed. Meaningful subnetworks enriched by breast cancer were identified.

Conclusion

A network-based integrative logistic regression model is proposed in the paper. It improves both the prediction and biomarker identification accuracy.

     

Probabilistic prediction and ranking of human protein-protein interactions

Background  

Although the prediction of protein-protein interactions has been extensively investigated for yeast, few such datasets exist for the far larger proteome in human. Furthermore, it has recently been estimated that the overall average false positive rate of available computational and high-throughput experimental interaction datasets is as high as 90%.     

Electric passenger car transport and passenger car life cycle inventories in ecoinvent version 3

Purpose

Due to the large environmental challenges posed by the transport sector, reliable and state-of-the art data for its life cycle assessment is essential for enabling a successful transition towards more sustainable systems. In this paper, the new electric passenger car transport and vehicle datasets, which have been developed for ecoinvent version 3, are presented.

Methods

The new datasets have been developed with a strong modular approach, defining a hierarchy of datasets corresponding to various technical components in the vehicle. A vehicle is therefore modelled by linking together the various component datasets. Also, parameters and mathematical formulas have been introduced in order to define the amount of exchanges in the datasets through common transport and vehicle characteristics. This supports users in the choice of the amount of exchanges and enhances the transparency of the dataset.

Results

The new transport dataset describes the transport over 1 km with a battery electric passenger car taking into account the vehicle production and end of life, the energy consumption due to the use phase, non-exhaust emissions, maintenance and road infrastructure. The dataset has been developed and is suitable for a compact class vehicle.

Conclusions

A new electric passenger car transport dataset has been developed for version 3 of the ecoinvent database which exploits modularisation and parameters with the aim of facilitating users in adapting the data to their specific needs. Apart from the direct use of the transport dataset for background data, the various datasets for the different components can also be used as building blocks for virtual vehicles.

     

Uncertainty analysis in LCA using precalculated aggregated datasets

Purpose

Some LCA software tools use precalculated aggregated datasets because they make LCA calculations much quicker. However, these datasets pose problems for uncertainty analysis. Even when aggregated dataset parameters are expressed as probability distributions, each dataset is sampled independently. This paper explores why independent sampling is incorrect and proposes two techniques to account for dependence in uncertainty analysis. The first is based on an analytical approach, while the other uses precalculated results sampled dependently.

Methods

The algorithm for generating arrays of dependently presampled aggregated inventories and their LCA scores is described. These arrays are used to calculate the correlation across all pairs of aggregated datasets in two ecoinvent LCI databases (2.2, 3.3 cutoff). The arrays are also used in the dependently presampled approach. The uncertainty of LCA results is calculated under different assumptions and using four different techniques and compared for two case studies: a simple water bottle LCA and an LCA of burger recipes.

Results and discussion

The meta-analysis of two LCI databases shows that there is no single correct approximation of correlation between aggregated datasets. The case studies show that the uncertainty of single-product LCA using aggregated datasets is usually underestimated when the correlation across datasets is ignored and that the magnitude of the underestimation is dependent on the system being analysed and the LCIA method chosen. Comparative LCA results show that independent sampling of aggregated datasets drastically overestimates the uncertainty of comparative metrics. The approach based on dependently presampled results yields results functionally identical to those obtained by Monte Carlo analysis using unit process datasets with a negligible computation time.

Conclusions

Independent sampling should not be used for comparative LCA. Moreover, the use of a one-size-fits-all correction factor to correct the calculated variability under independent sampling, as proposed elsewhere, is generally inadequate. The proposed approximate analytical approach is useful to estimate the importance of the covariance of aggregated datasets but not for comparative LCA. The approach based on dependently presampled results provides quick and correct results and has been implemented in EcodEX, a streamlined LCA software used by Nestlé. Dependently presampled results can be used for streamlined LCA software tools. Both presampling and analytical solutions require a preliminary one-time calculation of dependent samples for all aggregated datasets, which could be centrally done by database providers. The dependent presampling approach can be applied to other aspects of the LCA calculation chain.

     

OligoSpawn: a software tool for the design of overgo probes from large unigene datasets

Background  

Expressed sequence tag (EST) datasets represent perhaps the largest collection of genetic information. ESTs can be exploited in a variety of biological experiments and analysis. Here we are interested in the design of overlapping oligonucleotide (overgo) probes from large unigene (EST-contigs) datasets.     

Preferred analysis methods for Affymetrix GeneChips revealed by a wholly defined control dataset

Background  

As more methods are developed to analyze RNA-profiling data, assessing their performance using control datasets becomes increasingly important.     

A simulation study comparing supertree and combined analysis methods using SMIDGen

Background  

Supertree methods comprise one approach to reconstructing large molecular phylogenies given multi-marker datasets: trees are estimated on each marker and then combined into a tree (the "supertree") on the entire set of taxa. Supertrees can be constructed using various algorithmic techniques, with the most common being matrix representation with parsimony (MRP). When the data allow, the competing approach is a combined analysis (also known as a "supermatrix" or "total evidence" approach) whereby the different sequence data matrices for each of the different subsets of taxa are concatenated into a single supermatrix, and a tree is estimated on that supermatrix.     

Gene identification and protein classification in microbial metagenomic sequence data via incremental clustering

Background  

The identification and study of proteins from metagenomic datasets can shed light on the roles and interactions of the source organisms in their communities. However, metagenomic datasets are characterized by the presence of organisms with varying GC composition, codon usage biases etc., and consequently gene identification is challenging. The vast amount of sequence data also requires faster protein family classification tools.