Bayesian meta-analysis for identifying periodically expressed genes in fission yeast cell cycle

The effort to identify genes with periodic expression during the cell cycle from genome-wide microarray time series data has been ongoing for a decade. However, the lack of rigorous modeling of periodic expression as well as the lack of a comprehensive model for integrating information across genes and experiments has impaired the effort for the accurate identification of periodically expressed genes. To address the problem, we introduce a Bayesian model to integrate multiple independent microarray data sets from three recent genome-wide cell cycle studies on fission yeast. A hierarchical model was used for data integration. In order to facilitate an efficient Monte Carlo sampling from the joint posterior distribution, we develop a novel Metropolis--Hastings group move. A surprising finding from our integrated analysis is that more than 40% of the genes in fission yeast are significantly periodically expressed, greatly enhancing the reported 10--15% of the genes in the current literature. It calls for a reconsideration of the periodically expressed gene detection problem.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS300 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Ontology (Science)

Increasingly, in data-intensive areas of the life sciences, experimental results are being described in algorithmically useful ways with the help of ontologies. Such ontologies are authored and maintained by scientists to support the retrieval, integration and analysis of their data. The proposition to be defended here is that ontologies of this type – the Gene Ontology (GO) being the most conspicuous example – are a _part of science_. Initial evidence for the truth of this proposition (which some will find self-evident) is the increasing recognition of the importance of empirically-based methods of evaluation to the ontology develop¬ment work being undertaken in support of scientific research. Ontologies created by scientists must, of course, be associated with implementations satisfying the requirements of software engineering. But the ontologies are not themselves engineering artifacts, and to conceive them as such brings grievous consequences. Rather, ontologies such as the GO are in different respects comparable to scientific theories, to scientific databases, and to scientific journal publications. Such a view implies a new conception of what is involved in the author¬ing, maintenance and application of ontologies in scientific contexts, and therewith also a new approach to the evaluation of ontologies and to the training of ontologists

Stochastic Modeling of Expression Kinetics Identifies Messenger Half-Lives and Reveals Sequential Waves of Co-ordinated Transcription and Decay

The transcriptome in a cell is finely regulated by a large number of molecular mechanisms able to control the balance between mRNA production and degradation. Recent experimental findings have evidenced that fine and specific regulation of degradation is needed for proper orchestration of a global cell response to environmental conditions. We developed a computational technique based on stochastic modeling, to infer condition-specific individual mRNA half-lives directly from gene expression time-courses. Predictions from our method were validated by experimentally measured mRNA decay rates during the intraerythrocytic developmental cycle of Plasmodium falciparum. We then applied our methodology to publicly available data on the reproductive and metabolic cycle of budding yeast. Strikingly, our analysis revealed, in all cases, the presence of periodic changes in decay rates of sequentially induced genes and co-ordination strategies between transcription and degradation, thus suggesting a general principle for the proper coordination of transcription and degradation machinery in response to internal and/or external stimuli. Citation: Cacace F, Paci P, Cusimano V, Germani A, Farina L (2012) Stochastic Modeling of Expression Kinetics Identifies Messenger Half-Lives and Reveals Sequential Waves of Co-ordinated Transcription and Decay. PLoS Comput Biol 8(11): e1002772. doi:10.1371/journal.pcbi.100277

Unbiased Boolean analysis of public gene expression data for cell cycle gene identification.

Cell proliferation is essential for the development and maintenance of all organisms and is dysregulated in cancer. Using synchronized cells progressing through the cell cycle, pioneering microarray studies defined cell cycle genes based on cyclic variation in their expression. However, the concordance of the small number of synchronized cell studies has been limited, leading to discrepancies in definition of the transcriptionally regulated set of cell cycle genes within and between species. Here we present an informatics approach based on Boolean logic to identify cell cycle genes. This approach used the vast array of publicly available gene expression data sets to query similarity to CCNB1, which encodes the cyclin subunit of the Cdk1-cyclin B complex that triggers the G2-to-M transition. In addition to highlighting conservation of cell cycle genes across large evolutionary distances, this approach identified contexts where well-studied genes known to act during the cell cycle are expressed and potentially acting in nondivision contexts. An accessible web platform enables a detailed exploration of the cell cycle gene lists generated using the Boolean logic approach. The methods employed are straightforward to extend to processes other than the cell cycle

Graph Theory and Networks in Biology

In this paper, we present a survey of the use of graph theoretical techniques in Biology. In particular, we discuss recent work on identifying and modelling the structure of bio-molecular networks, as well as the application of centrality measures to interaction networks and research on the hierarchical structure of such networks and network motifs. Work on the link between structural network properties and dynamics is also described, with emphasis on synchronization and disease propagation.Comment: 52 pages, 5 figures, Survey Pape

Synthesis of time-to-amplitude converter by mean coevolution with adaptive parameters

Copyright © 2011 the authors and Scientific Research Publishing Inc. This work is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)The challenging task to synthesize automatically a time-to-amplitude converter, which unites by its functionality several digital circuits, has been successfully solved with the help of a novel methodology. The proposed approach is based on a paradigm according to which the substructures are regarded as additional mutation types and when ranged with other mutations form a new adaptive individual-level mutation technique. This mutation approach led to the discovery of an original coevolution strategy that is characterized by very low selection rates. Parallel island-model evolution has been running in a hybrid competitive-cooperative interaction throughout two incremental stages. The adaptive population size is applied for synchronization of the parallel evolutions

VizRank: Data Visualization Guided by Machine Learning

Data visualization plays a crucial role in identifying interesting patterns in exploratory data analysis. Its use is, however, made difficult by the large number of possible data projections showing different attribute subsets that must be evaluated by the data analyst. In this paper, we introduce a method called VizRank, which is applied on classified data to automatically select the most useful data projections. VizRank can be used with any visualization method that maps attribute values to points in a two-dimensional visualization space. It assesses possible data projections and ranks them by their ability to visually discriminate between classes. The quality of class separation is estimated by computing the predictive accuracy of k-nearest neighbor classifier on the data set consisting of x and y positions of the projected data points and their class information. The paper introduces the method and presents experimental results which show that VizRank's ranking of projections highly agrees with subjective rankings by data analysts. The practical use of VizRank is also demonstrated by an application in the field of functional genomics

Hopfield Networks in Relevance and Redundancy Feature Selection Applied to Classification of Biomedical High-Resolution Micro-CT Images

We study filter–based feature selection methods for classification of biomedical images. For feature selection, we use two filters — a relevance filter which measures usefulness of individual features for target prediction, and a redundancy filter, which measures similarity between features. As selection method that combines relevance and redundancy we try out a Hopfield network. We experimentally compare selection methods, running unitary redundancy and relevance filters, against a greedy algorithm with redundancy thresholds [9], the min-redundancy max-relevance integration [8,23,36], and our Hopfield network selection. We conclude that on the whole, Hopfield selection was one of the most successful methods, outperforming min-redundancy max-relevance when\ud more features are selected