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2.  Obituary: Professor Paul Dan Cristea 
Paul Dan Cristea, professor of Electrical Engineering and Computer Science at ‘Politehnica’ University of Bucharest died on 17 April 2013, following several years of bravely battling a perfidious illness.
doi:10.1186/1687-4153-2013-7
PMCID: PMC3656793  PMID: 23663854
3.  Reverse Engineering Sparse Gene Regulatory Networks Using Cubature Kalman Filter and Compressed Sensing 
Advances in Bioinformatics  2013;2013:205763.
This paper proposes a novel algorithm for inferring gene regulatory networks which makes use of cubature Kalman filter (CKF) and Kalman filter (KF) techniques in conjunction with compressed sensing methods. The gene network is described using a state-space model. A nonlinear model for the evolution of gene expression is considered, while the gene expression data is assumed to follow a linear Gaussian model. The hidden states are estimated using CKF. The system parameters are modeled as a Gauss-Markov process and are estimated using compressed sensing-based KF. These parameters provide insight into the regulatory relations among the genes. The Cramér-Rao lower bound of the parameter estimates is calculated for the system model and used as a benchmark to assess the estimation accuracy. The proposed algorithm is evaluated rigorously using synthetic data in different scenarios which include different number of genes and varying number of sample points. In addition, the algorithm is tested on the DREAM4 in silico data sets as well as the in vivo data sets from IRMA network. The proposed algorithm shows superior performance in terms of accuracy, robustness, and scalability.
doi:10.1155/2013/205763
PMCID: PMC3664478  PMID: 23737768
4.  Spectral Analysis on Time-Course Expression Data: Detecting Periodic Genes Using a Real-Valued Iterative Adaptive Approach 
Advances in Bioinformatics  2013;2013:171530.
Time-course expression profiles and methods for spectrum analysis have been applied for detecting transcriptional periodicities, which are valuable patterns to unravel genes associated with cell cycle and circadian rhythm regulation. However, most of the proposed methods suffer from restrictions and large false positives to a certain extent. Additionally, in some experiments, arbitrarily irregular sampling times as well as the presence of high noise and small sample sizes make accurate detection a challenging task. A novel scheme for detecting periodicities in time-course expression data is proposed, in which a real-valued iterative adaptive approach (RIAA), originally proposed for signal processing, is applied for periodogram estimation. The inferred spectrum is then analyzed using Fisher's hypothesis test. With a proper p-value threshold, periodic genes can be detected. A periodic signal, two nonperiodic signals, and four sampling strategies were considered in the simulations, including both bursts and drops. In addition, two yeast real datasets were applied for validation. The simulations and real data analysis reveal that RIAA can perform competitively with the existing algorithms. The advantage of RIAA is manifested when the expression data are highly irregularly sampled, and when the number of cycles covered by the sampling time points is very reduced.
doi:10.1155/2013/171530
PMCID: PMC3600260  PMID: 23533399
5.  An Overview of the Statistical Methods Used for Inferring Gene Regulatory Networks and Protein-Protein Interaction Networks 
Advances in Bioinformatics  2013;2013:953814.
The large influx of data from high-throughput genomic and proteomic technologies has encouraged the researchers to seek approaches for understanding the structure of gene regulatory networks and proteomic networks. This work reviews some of the most important statistical methods used for modeling of gene regulatory networks (GRNs) and protein-protein interaction (PPI) networks. The paper focuses on the recent advances in the statistical graphical modeling techniques, state-space representation models, and information theoretic methods that were proposed for inferring the topology of GRNs. It appears that the problem of inferring the structure of PPI networks is quite different from that of GRNs. Clustering and probabilistic graphical modeling techniques are of prime importance in the statistical inference of PPI networks, and some of the recent approaches using these techniques are also reviewed in this paper. Performance evaluation criteria for the approaches used for modeling GRNs and PPI networks are also discussed.
doi:10.1155/2013/953814
PMCID: PMC3594945  PMID: 23509452
6.  Optimal reference sequence selection for genome assembly using minimum description length principle 
Reference assisted assembly requires the use of a reference sequence, as a model, to assist in the assembly of the novel genome. The standard method for identifying the best reference sequence for the assembly of a novel genome aims at counting the number of reads that align to the reference sequence, and then choosing the reference sequence which has the highest number of reads aligning to it. This article explores the use of minimum description length (MDL) principle and its two variants, the two-part MDL and Sophisticated MDL, in identifying the optimal reference sequence for genome assembly. The article compares the MDL based proposed scheme with the standard method coming to the conclusion that “counting the number of reads of the novel genome present in the reference sequence” is not a sufficient condition. Therefore, the proposed MDL scheme includes within itself the standard method of “counting the number of reads that align to the reference sequence” and also moves forward towards looking at the model, the reference sequence, as well, in identifying the optimal reference sequence. The proposed MDL based scheme not only becomes the sufficient criterion for identifying the optimal reference sequence for genome assembly but also improves the reference sequence so that it becomes more suitable for the assembly of the novel genome.
doi:10.1186/1687-4153-2012-18
PMCID: PMC3608252  PMID: 23186305
7.  Reducing confounding and suppression effects in TCGA data: an integrated analysis of chemotherapy response in ovarian cancer 
BMC Genomics  2012;13(Suppl 6):S13.
Background
Despite initial response in adjuvant chemotherapy, ovarian cancer patients treated with the combination of paclitaxel and carboplatin frequently suffer from recurrence after few cycles of treatment, and the underlying mechanisms causing the chemoresistance remain unclear. Recently, The Cancer Genome Atlas (TCGA) research network concluded an ovarian cancer study and released the dataset to the public. The TCGA dataset possesses large sample size, comprehensive molecular profiles, and clinical outcome information; however, because of the unknown molecular subtypes in ovarian cancer and the great diversity of adjuvant treatments TCGA patients went through, studying chemotherapeutic response using the TCGA data is difficult. Additionally, factors such as sample batches, patient ages, and tumor stages further confound or suppress the identification of relevant genes, and thus the biological functions and disease mechanisms.
Results
To address these issues, herein we propose an analysis procedure designed to reduce suppression effect by focusing on a specific chemotherapeutic treatment, and to remove confounding effects such as batch effect, patient's age, and tumor stages. The proposed procedure starts with a batch effect adjustment, followed by a rigorous sample selection process. Then, the gene expression, copy number, and methylation profiles from the TCGA ovarian cancer dataset are analyzed using a semi-supervised clustering method combined with a novel scoring function. As a result, two molecular classifications, one with poor copy number profiles and one with poor methylation profiles, enriched with unfavorable scores are identified. Compared with the samples enriched with favorable scores, these two classifications exhibit poor progression-free survival (PFS) and might be associated with poor chemotherapy response specifically to the combination of paclitaxel and carboplatin. Significant genes and biological processes are detected subsequently using classical statistical approaches and enrichment analysis.
Conclusions
The proposed procedure for the reduction of confounding and suppression effects and the semi-supervised clustering method are essential steps to identify genes associated with the chemotherapeutic response.
doi:10.1186/1471-2164-13-S6-S13
PMCID: PMC3481440  PMID: 23134756
9.  Identifying Genes Involved in Cyclic Processes by Combining Gene Expression Analysis and Prior Knowledge 
Based on time series gene expressions, cyclic genes can be recognized via spectral analysis and statistical periodicity detection tests. These cyclic genes are usually associated with cyclic biological processes, for example, cell cycle and circadian rhythm. The power of a scheme is practically measured by comparing the detected periodically expressed genes with experimentally verified genes participating in a cyclic process. However, in the above mentioned procedure the valuable prior knowledge only serves as an evaluation benchmark, and it is not fully exploited in the implementation of the algorithm. In addition, partial data sets are also disregarded due to their nonstationarity. This paper proposes a novel algorithm to identify cyclic-process-involved genes by integrating the prior knowledge with the gene expression analysis. The proposed algorithm is applied on data sets corresponding to Saccharomyces cerevisiae and Drosophila melanogaster, respectively. Biological evidences are found to validate the roles of the discovered genes in cell cycle and circadian rhythm. Dendrograms are presented to cluster the identified genes and to reveal expression patterns. It is corroborated that the proposed novel identification scheme provides a valuable technique for unveiling pathways related to cyclic processes.
doi:10.1155/2009/683463
PMCID: PMC3171438  PMID: 19390635
10.  Spectral Preprocessing for Clustering Time-Series Gene Expressions 
Based on gene expression profiles, genes can be partitioned into clusters, which might be associated with biological processes or functions, for example, cell cycle, circadian rhythm, and so forth. This paper proposes a novel clustering preprocessing strategy which combines clustering with spectral estimation techniques so that the time information present in time series gene expressions is fully exploited. By comparing the clustering results with a set of biologically annotated yeast cell-cycle genes, the proposed clustering strategy is corroborated to yield significantly different clusters from those created by the traditional expression-based schemes. The proposed technique is especially helpful in grouping genes participating in time-regulated processes.
doi:10.1155/2009/713248
PMCID: PMC3171439  PMID: 19381338
11.  Clock Synchronization in Wireless Sensor Networks: An Overview 
Sensors (Basel, Switzerland)  2009;9(1):56-85.
The development of tiny, low-cost, low-power and multifunctional sensor nodes equipped with sensing, data processing, and communicating components, have been made possible by the recent advances in micro-electro-mechanical systems (MEMS) technology. Wireless sensor networks (WSNs) assume a collection of such tiny sensing devices connected wirelessly and which are used to observe and monitor a variety of phenomena in the real physical world. Many applications based on these WSNs assume local clocks at each sensor node that need to be synchronized to a common notion of time. This paper reviews the existing clock synchronization protocols for WSNs and the methods of estimating clock offset and clock skew in the most representative clock synchronization protocols for WSNs.
doi:10.3390/s90100056
PMCID: PMC3280734  PMID: 22389588
Wireless sensor networks; Clock synchronization; Clock offset; Clock skew
12.  Recovering Genetic Regulatory Networks from Chromatin Immunoprecipitation and Steady-State Microarray Data 
Recent advances in high-throughput DNA microarrays and chromatin immunoprecipitation (ChIP) assays have enabled the learning of the structure and functionality of genetic regulatory networks. In light of these heterogeneous data sets, this paper proposes a novel approach for reconstruction of genetic regulatory networks based on the posterior probabilities of gene regulations. Built within the framework of Bayesian statistics and computational Monte Carlo techniques, the proposed approach prevents the dichotomy of classifying gene interactions as either being connected or disconnected, thereby it reduces significantly the inference errors. Simulation results corroborate the superior performance of the proposed approach relative to the existing state-of-the-art algorithms. A genetic regulatory network for Saccharomyces cerevisiae is inferred based on the published real data sets, and biological meaningful results are discussed.
doi:10.1155/2008/248747
PMCID: PMC3171391  PMID: 18584039
13.  Detecting Periodic Genes from Irregularly Sampled Gene Expressions: A Comparison Study 
Time series microarray measurements of gene expressions have been exploited to discover genes involved in cell cycles. Due to experimental constraints, most microarray observations are obtained through irregular sampling. In this paper three popular spectral analysis schemes, namely, Lomb-Scargle, Capon and missing-data amplitude and phase estimation (MAPES), are compared in terms of their ability and efficiency to recover periodically expressed genes. Based on in silico experiments for microarray measurements of Saccharomyces cerevisiae, Lomb-Scargle is found to be the most efficacious scheme. 149 genes are then identified to be periodically expressed in the Drosophila melanogaster data set.
doi:10.1155/2008/769293
PMCID: PMC3171399  PMID: 18584052

Results 1-13 (13)