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Thuc Le

University of South Australia, School of IT and Mathematical Science, Faculty Member

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Jordi Vallverdú

Universitat Autònoma de Barcelona

Jayjit Majumdar

University of Kalyani

Amrita Vishwa Vidyapeetham

Kansas State University

Prof. Mohamed Labib Salem

Tanta University

Samit Chakrabarty

University of Leeds

Richard Sullivan

King's College London

Michael J. Gonzalez

Universidad de Puerto Rico Rio

Dr.Yousery Sherif

Mansoura University

North Carolina State University

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Papers by Thuc Le

Identification of miRNA-mRNA regulatory modules by exploring collective group relationships

BMC genomics, Jan 11, 2016

microRNAs (miRNAs) play an essential role in the post-transcriptional gene regulation in plants a... more microRNAs (miRNAs) play an essential role in the post-transcriptional gene regulation in plants and animals. They regulate a wide range of biological processes by targeting messenger RNAs (mRNAs). Evidence suggests that miRNAs and mRNAs interact collectively in gene regulatory networks. The collective relationships between groups of miRNAs and groups of mRNAs may be more readily interpreted than those between individual miRNAs and mRNAs, and thus are useful for gaining insight into gene regulation and cell functions. Several computational approaches have been developed to discover miRNA-mRNA regulatory modules (MMRMs) with a common aim to elucidate miRNA-mRNA regulatory relationships. However, most existing methods do not consider the collective relationships between a group of miRNAs and the group of targeted mRNAs in the process of discovering MMRMs. Our aim is to develop a framework to discover MMRMs and reveal miRNA-mRNA regulatory relationships from the heterogeneous expression...

Identifying miRNA synergistic regulatory network in heterogeneous human data via network motifs

Mol. BioSyst., 2015

We present a causality based framework called mirSRN to infer miRNA synergism in human molecular ... more

Mining combined causes in large data sets

Knowledge-Based Systems, 2015

Computational methods for identifying miRNA sponge interactions

by Thuc Le and Jiuyong Li

Briefings in bioinformatics, Jan 5, 2016

Recent findings show that coding genes are not the only targets that miRNAs interact with. In fac... more Recent findings show that coding genes are not the only targets that miRNAs interact with. In fact, there is a pool of different RNAs competing with each other to attract miRNAs for interactions, thus acting as competing endogenous RNAs (ceRNAs). The ceRNAs indirectly regulate each other via the titration mechanism, i.e. the increasing concentration of a ceRNA will decrease the number of miRNAs that are available for interacting with other targets. The cross-talks between ceRNAs, i.e. their interactions mediated by miRNAs, have been identified as the drivers in many disease conditions, including cancers. In recent years, some computational methods have emerged for identifying ceRNA-ceRNA interactions. However, there remain great challenges and opportunities for developing computational methods to provide new insights into ceRNA regulatory mechanisms.In this paper, we review the publically available databases of ceRNA-ceRNA interactions and the computational methods for identifying c...

Predicting miRNA Targets by Integrating Gene Regulatory Knowledge with Expression Profiles

by Weijia Zhang, Thuc Le, and Jiuyong Li

PloS one, 2016

microRNAs (miRNAs) play crucial roles in post-transcriptional gene regulation of both plants and ... more microRNAs (miRNAs) play crucial roles in post-transcriptional gene regulation of both plants and mammals, and dysfunctions of miRNAs are often associated with tumorigenesis and development through the effects on their target messenger RNAs (mRNAs). Identifying miRNA functions is critical for understanding cancer mechanisms and determining the efficacy of drugs. Computational methods analyzing high-throughput data offer great assistance in understanding the diverse and complex relationships between miRNAs and mRNAs. However, most of the existing methods do not fully utilise the available knowledge in biology to reduce the uncertainty in the modeling process. Therefore it is desirable to develop a method that can seamlessly integrate existing biological knowledge and high-throughput data into the process of discovering miRNA regulation mechanisms. In this article we present an integrative framework, CIDER (Causal miRNA target Discovery with Expression profile and Regulatory knowledge)...

miRLAB: An R Based Dry Lab for Exploring miRNA-mRNA Regulatory Relationships

by Thuc Le and Jiuyong Li

PloS one, 2015

microRNAs (miRNAs) are important gene regulators at post-transcriptional level, and inferring miR... more microRNAs (miRNAs) are important gene regulators at post-transcriptional level, and inferring miRNA-mRNA regulatory relationships is a crucial problem. Consequently, several computational methods of predicting miRNA targets have been proposed using expression data with or without sequence based miRNA target information. A typical procedure for applying and evaluating such a method is i) collecting matched miRNA and mRNA expression profiles in a specific condition, e.g. a cancer dataset from The Cancer Genome Atlas (TCGA), ii) applying the new computational method to the selected dataset, iii) validating the predictions against knowledge from literature and third-party databases, and comparing the performance of the method with some existing methods. This procedure is time consuming given the time elapsed when collecting and processing data, repeating the work from existing methods, searching for knowledge from literature and third-party databases to validate the results, and compari...

A novel framework for inferring condition-specific TF and miRNA co-regulation of protein-protein interactions

Gene, Jan 20, 2015

Recent studies have shown that transcription factors (TFs) and microRNAs (miRNAs), while independ... more Recent studies have shown that transcription factors (TFs) and microRNAs (miRNAs), while independently regulate their downstream targets, collaborate with each other to regulate gene expression. However, their synergistic roles in protein-protein interactions (PPIs) remain mostly unknown. In this paper, we present a novel framework (called CoRePPI) for inferring TF and miRNA co-regulation of PPIs. Particularly, CoRePPI is aimed at discovering the co-regulation specific to a condition of interest, by using heterogeneous data, including miRNA and messenger RNA (mRNA) expression profiles, putative miRNA targets, TF targets and PPIs. CoRePPI firstly finds the network motifs indicating the co-regulation of PPIs by TFs and miRNAs in tumor and normal conditions separately. Then by identifying the differential motifs found in one condition but not in the other, it builds the networks consisting of TFs, miRNAs and their co-regulated PPIs specific to different conditions respectively. To vali...

Ensemble Methods for MiRNA Target Prediction from Expression Data

by Junpeng Zhang, Thuc Le, and Jiuyong Li

PLOS ONE, 2015

microRNAs (miRNAs) are short regulatory RNAs that are involved in several diseases, including can... more microRNAs (miRNAs) are short regulatory RNAs that are involved in several diseases, including cancers. Identifying miRNA functions is very important in understanding disease mechanisms and determining the efficacy of drugs. An increasing number of computational methods have been developed to explore miRNA functions by inferring the miRNA-mRNA regulatory relationships from data. Each of the methods is developed based on some assumptions and constraints, for instance, assuming linear relationships between variables. For such reasons, computational methods are often subject to the problem of inconsistent performance across different datasets. On the other hand, ensemble methods integrate the results from individual methods and have been proved to outperform each of their individual component methods in theory. In this paper, we investigate the performance of some ensemble methods over the commonly used miRNA target prediction methods. We apply eight different popular miRNA target prediction methods to three cancer datasets, and compare their performance with the ensemble methods which integrate the results from each combination of the individual methods. The validation results using experimentally confirmed databases show that the results of the ensemble methods complement those obtained by the individual methods and the ensemble methods perform better than the individual methods across different datasets. The ensemble method, Pearson+IDA+Lasso, which combines methods in different approaches, including a correlation method, a causal inference method, and a regression method, is the best performed ensemble method in this study. Further analysis of the results of this ensemble method shows that the ensemble method can obtain more targets which could not be found by any of the single methods, and the discovered targets are more statistically significant and functionally enriched. The source codes, datasets, miRNA target predictions by all methods, and the ground truth for validation are available in the Supplementary materials.

ConditionSpecificMirnaActivity

ConditionSpecificSupp

From miRNA regulation to miRNA-TF co-regulation: computational approaches and challenges

by Thuc Le and Jiuyong Li

Briefings in bioinformatics, Jan 12, 2014

microRNAs (miRNAs) are important gene regulators. They control a wide range of biological process... more microRNAs (miRNAs) are important gene regulators. They control a wide range of biological processes and are involved in several types of cancers. Thus, exploring miRNA functions is important for diagnostics and therapeutics. To date, there are few feasible experimental techniques for discovering miRNA regulatory mechanisms. Alternatively, predictions of miRNA-mRNA regulatory relationships by computational methods have increasingly achieved promising results. Computational approaches are proving their ability as effective tools in reducing the number of biological experiments that must be conducted and to assist with the design of the experiments. In this review, we categorize and review different computational approaches to identify miRNA activities and functions, including the co-regulation of miRNAs and transcription factors. Our main focuses are on the recent approaches that use multiple data types for exploring miRNA functions. We discuss the remaining challenges in the evaluati...

Inferring condition-specific miRNA activity from matched miRNA and mRNA expression data

by Thuc Le and Jiuyong Li

Bioinformatics (Oxford, England), 2014

MicroRNAs (miRNAs) play crucial roles in complex cellular networks by binding to the messenger RN... more MicroRNAs (miRNAs) play crucial roles in complex cellular networks by binding to the messenger RNAs (mRNAs) of protein coding genes. It has been found that miRNA regulation is often condition-specific. A number of computational approaches have been developed to identify miRNA activity specific to a condition of interest using gene expression data. However, most of the methods only use the data in a single condition, and thus, the activity discovered may not be unique to the condition of interest. Additionally, these methods are based on statistical associations between the gene expression levels of miRNAs and mRNAs, so they may not be able to reveal real gene regulatory relationships, which are causal relationships. We propose a novel method to infer condition-specific miRNA activity by considering (i) the difference between the regulatory behavior that an miRNA has in the condition of interest and its behavior in the other conditions; (ii) the causal semantics of miRNA-mRNA relatio...

Identifying direct miRNA–mRNA causal regulatory relationships in heterogeneous data

by Thuc Le and Jiuyong Li

Journal of Biomedical Informatics, 2014

Discovering the regulatory relationships between microRNAs (miRNAs) and mRNAs is an important pro... more Discovering the regulatory relationships between microRNAs (miRNAs) and mRNAs is an important problem that interests many biologists and medical researchers. A number of computational methods have been proposed to infer miRNA-mRNA regulatory relationships, and are mostly based on the statistical associations between miRNAs and mRNAs discovered in observational data. The miRNA-mRNA regulatory relationships identified by these methods can be both direct and indirect regulations. However, differentiating direct regulatory relationships from indirect ones is important for biologists in experimental designs. In this paper, we present a causal discovery based framework (called DirectTarget) to infer direct miRNA-mRNA causal regulatory relationships in heterogeneous data, including expression profiles of miRNAs and mRNAs, and miRNA target information. DirectTarget is applied to the Epithelial to Mesenchymal Transition (EMT) datasets. The validation by experimentally confirmed target databases suggests that the proposed method can effectively identify direct miRNA-mRNA regulatory relationships. To explore the upstream regulators of miRNA regulation, we further identify the causal feedforward patterns (CFFPs) of TF-miRNA-mRNA to provide insights into the miRNA regulation in EMT. DirectTarget has the potential to be applied to other datasets to elucidate the direct miRNA-mRNA causal regulatory relationships and to explore the regulatory patterns.

A Local Causal Discovery Algorithm for High Dimensional Data

SpringerBriefs in Electrical and Computer Engineering, 2015

Causal Rule Discovery with Partial Association Test

by Thuc Le and Jiuyong Li

SpringerBriefs in Electrical and Computer Engineering, 2015

Causal Rule Discovery with Cohort Studies

SpringerBriefs in Electrical and Computer Engineering, 2015

Experimental Comparison and Discussions

by Thuc Le and Jiuyong Li

SpringerBriefs in Electrical and Computer Engineering, 2015

A fast PC algorithm for high dimensional causal discovery with multi-core PCs

by Thuc Le and Jiuyong Li

Discovering causal relationships from observational data is a crucial problem and it has applicat... more Discovering causal relationships from observational data is a crucial problem and it has applications in many research areas. The PC algorithm is the state-of-the-art constraint based method for causal discovery. However, runtime of the PC algorithm, in the worst-case, is exponential to the number of nodes (variables), and thus it is inefficient when being applied to high dimensional data, e.g. gene expression datasets. On another note, the advancement of computer hardware in the last decade has resulted in the widespread availability of multi-core personal computers. There is a significant motivation for designing a parallelised PC algorithm that is suitable for personal computers and does not require end users&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; parallel computing knowledge beyond their competency in using the PC algorithm. In this paper, we develop parallel-PC, a fast and memory efficient PC algorithm using the parallel computing technique. We apply our method to a range of synthetic and real-world high dimensional datasets. Experimental results on a dataset from the DREAM 5 challenge show that the original PC algorithm could not produce any results after running more than 24 hours; meanwhile, our parallel-PC algorithm managed to finish within around 12 hours with a 4-core CPU computer, and less than 6 hours with a 8-core CPU computer. Furthermore, we integrate parallel-PC into a causal inference method for inferring miRNA-mRNA regulatory relationships. The experimental results show that parallel-PC helps improve both the efficiency and accuracy of the causal inference algorithm.

Discovery of Causal Rules Using Partial Association

by Thuc Le and Jiuyong Li

2012 IEEE 12th International Conference on Data Mining, 2012

ABSTRACT Discovering causal relationships in large databases of observational data is challenging... more ABSTRACT Discovering causal relationships in large databases of observational data is challenging. The pioneering work in this area was rooted in the theory of Bayesian network (BN) learning, which however, is a NP-complete problem. Hence several constraint-based algorithms have been developed to efficiently discover causations in large databases. These methods usually use the idea of BN learning, directly or indirectly, and are focused on causal relationships with single cause variables. In this paper, we propose an approach to mine causal rules in large databases of binary variables. Our method expands the scope of causality discovery to causal relationships with multiple cause variables, and we utilise partial association tests to exclude noncausal associations, to ensure the high reliability of discovered causal rules. Furthermore an efficient algorithm is designed for the tests in large databases. We assess the method with a set of real-world diagnostic data. The results show that our method can effectively discover interesting causal rules in large databases.

Mining Causal Association Rules

2013 IEEE 13th International Conference on Data Mining Workshops, 2013

ABSTRACT Discovering causal relationships is the ultimate goal of many scientific explorations. C... more ABSTRACT Discovering causal relationships is the ultimate goal of many scientific explorations. Causal relationships can be identified with controlled experiments, but such experiments are often very expensive and sometimes impossible to conduct. On the other hand, the collection of observational data has increased dramatically in recent decades. Therefore it is desirable to find causal relationships from the data directly. Significant progress has been made in the field of discovering causal relationships using the Causal Bayesian Network (CBN) theory. The applications of CBNs, however, are greatly limited due to the high computational complexity. In another direction, association rule mining has been shown to be an efficient data mining means for relationship discovery. However, although causal relationships imply associations, the reverse does not always hold. In this paper we study how to use an efficient association mining approach to discover potential causal rules in observational data. We make use of the idea of retrospective cohort studies, a widely used approach in medical and social research, to detect causal association rules. In comparison with the constraint-based methods within the CBN paradigm, the proposed approach is faster and is capable of finding a cause consisting of combined variables.

Identification of miRNA-mRNA regulatory modules by exploring collective group relationships

BMC genomics, Jan 11, 2016

microRNAs (miRNAs) play an essential role in the post-transcriptional gene regulation in plants a... more microRNAs (miRNAs) play an essential role in the post-transcriptional gene regulation in plants and animals. They regulate a wide range of biological processes by targeting messenger RNAs (mRNAs). Evidence suggests that miRNAs and mRNAs interact collectively in gene regulatory networks. The collective relationships between groups of miRNAs and groups of mRNAs may be more readily interpreted than those between individual miRNAs and mRNAs, and thus are useful for gaining insight into gene regulation and cell functions. Several computational approaches have been developed to discover miRNA-mRNA regulatory modules (MMRMs) with a common aim to elucidate miRNA-mRNA regulatory relationships. However, most existing methods do not consider the collective relationships between a group of miRNAs and the group of targeted mRNAs in the process of discovering MMRMs. Our aim is to develop a framework to discover MMRMs and reveal miRNA-mRNA regulatory relationships from the heterogeneous expression...

Identifying miRNA synergistic regulatory network in heterogeneous human data via network motifs

Mol. BioSyst., 2015

We present a causality based framework called mirSRN to infer miRNA synergism in human molecular ... more

Mining combined causes in large data sets

Knowledge-Based Systems, 2015

Computational methods for identifying miRNA sponge interactions

by Thuc Le and Jiuyong Li

Briefings in bioinformatics, Jan 5, 2016

Recent findings show that coding genes are not the only targets that miRNAs interact with. In fac... more Recent findings show that coding genes are not the only targets that miRNAs interact with. In fact, there is a pool of different RNAs competing with each other to attract miRNAs for interactions, thus acting as competing endogenous RNAs (ceRNAs). The ceRNAs indirectly regulate each other via the titration mechanism, i.e. the increasing concentration of a ceRNA will decrease the number of miRNAs that are available for interacting with other targets. The cross-talks between ceRNAs, i.e. their interactions mediated by miRNAs, have been identified as the drivers in many disease conditions, including cancers. In recent years, some computational methods have emerged for identifying ceRNA-ceRNA interactions. However, there remain great challenges and opportunities for developing computational methods to provide new insights into ceRNA regulatory mechanisms.In this paper, we review the publically available databases of ceRNA-ceRNA interactions and the computational methods for identifying c...

Predicting miRNA Targets by Integrating Gene Regulatory Knowledge with Expression Profiles

by Weijia Zhang, Thuc Le, and Jiuyong Li

PloS one, 2016

microRNAs (miRNAs) play crucial roles in post-transcriptional gene regulation of both plants and ... more microRNAs (miRNAs) play crucial roles in post-transcriptional gene regulation of both plants and mammals, and dysfunctions of miRNAs are often associated with tumorigenesis and development through the effects on their target messenger RNAs (mRNAs). Identifying miRNA functions is critical for understanding cancer mechanisms and determining the efficacy of drugs. Computational methods analyzing high-throughput data offer great assistance in understanding the diverse and complex relationships between miRNAs and mRNAs. However, most of the existing methods do not fully utilise the available knowledge in biology to reduce the uncertainty in the modeling process. Therefore it is desirable to develop a method that can seamlessly integrate existing biological knowledge and high-throughput data into the process of discovering miRNA regulation mechanisms. In this article we present an integrative framework, CIDER (Causal miRNA target Discovery with Expression profile and Regulatory knowledge)...

miRLAB: An R Based Dry Lab for Exploring miRNA-mRNA Regulatory Relationships

by Thuc Le and Jiuyong Li

PloS one, 2015

microRNAs (miRNAs) are important gene regulators at post-transcriptional level, and inferring miR... more microRNAs (miRNAs) are important gene regulators at post-transcriptional level, and inferring miRNA-mRNA regulatory relationships is a crucial problem. Consequently, several computational methods of predicting miRNA targets have been proposed using expression data with or without sequence based miRNA target information. A typical procedure for applying and evaluating such a method is i) collecting matched miRNA and mRNA expression profiles in a specific condition, e.g. a cancer dataset from The Cancer Genome Atlas (TCGA), ii) applying the new computational method to the selected dataset, iii) validating the predictions against knowledge from literature and third-party databases, and comparing the performance of the method with some existing methods. This procedure is time consuming given the time elapsed when collecting and processing data, repeating the work from existing methods, searching for knowledge from literature and third-party databases to validate the results, and compari...

A novel framework for inferring condition-specific TF and miRNA co-regulation of protein-protein interactions

Gene, Jan 20, 2015

Recent studies have shown that transcription factors (TFs) and microRNAs (miRNAs), while independ... more Recent studies have shown that transcription factors (TFs) and microRNAs (miRNAs), while independently regulate their downstream targets, collaborate with each other to regulate gene expression. However, their synergistic roles in protein-protein interactions (PPIs) remain mostly unknown. In this paper, we present a novel framework (called CoRePPI) for inferring TF and miRNA co-regulation of PPIs. Particularly, CoRePPI is aimed at discovering the co-regulation specific to a condition of interest, by using heterogeneous data, including miRNA and messenger RNA (mRNA) expression profiles, putative miRNA targets, TF targets and PPIs. CoRePPI firstly finds the network motifs indicating the co-regulation of PPIs by TFs and miRNAs in tumor and normal conditions separately. Then by identifying the differential motifs found in one condition but not in the other, it builds the networks consisting of TFs, miRNAs and their co-regulated PPIs specific to different conditions respectively. To vali...

Ensemble Methods for MiRNA Target Prediction from Expression Data

by Junpeng Zhang, Thuc Le, and Jiuyong Li

PLOS ONE, 2015

microRNAs (miRNAs) are short regulatory RNAs that are involved in several diseases, including can... more microRNAs (miRNAs) are short regulatory RNAs that are involved in several diseases, including cancers. Identifying miRNA functions is very important in understanding disease mechanisms and determining the efficacy of drugs. An increasing number of computational methods have been developed to explore miRNA functions by inferring the miRNA-mRNA regulatory relationships from data. Each of the methods is developed based on some assumptions and constraints, for instance, assuming linear relationships between variables. For such reasons, computational methods are often subject to the problem of inconsistent performance across different datasets. On the other hand, ensemble methods integrate the results from individual methods and have been proved to outperform each of their individual component methods in theory. In this paper, we investigate the performance of some ensemble methods over the commonly used miRNA target prediction methods. We apply eight different popular miRNA target prediction methods to three cancer datasets, and compare their performance with the ensemble methods which integrate the results from each combination of the individual methods. The validation results using experimentally confirmed databases show that the results of the ensemble methods complement those obtained by the individual methods and the ensemble methods perform better than the individual methods across different datasets. The ensemble method, Pearson+IDA+Lasso, which combines methods in different approaches, including a correlation method, a causal inference method, and a regression method, is the best performed ensemble method in this study. Further analysis of the results of this ensemble method shows that the ensemble method can obtain more targets which could not be found by any of the single methods, and the discovered targets are more statistically significant and functionally enriched. The source codes, datasets, miRNA target predictions by all methods, and the ground truth for validation are available in the Supplementary materials.

ConditionSpecificMirnaActivity

ConditionSpecificSupp

From miRNA regulation to miRNA-TF co-regulation: computational approaches and challenges

by Thuc Le and Jiuyong Li

Briefings in bioinformatics, Jan 12, 2014

microRNAs (miRNAs) are important gene regulators. They control a wide range of biological process... more microRNAs (miRNAs) are important gene regulators. They control a wide range of biological processes and are involved in several types of cancers. Thus, exploring miRNA functions is important for diagnostics and therapeutics. To date, there are few feasible experimental techniques for discovering miRNA regulatory mechanisms. Alternatively, predictions of miRNA-mRNA regulatory relationships by computational methods have increasingly achieved promising results. Computational approaches are proving their ability as effective tools in reducing the number of biological experiments that must be conducted and to assist with the design of the experiments. In this review, we categorize and review different computational approaches to identify miRNA activities and functions, including the co-regulation of miRNAs and transcription factors. Our main focuses are on the recent approaches that use multiple data types for exploring miRNA functions. We discuss the remaining challenges in the evaluati...

Inferring condition-specific miRNA activity from matched miRNA and mRNA expression data

by Thuc Le and Jiuyong Li

Bioinformatics (Oxford, England), 2014

MicroRNAs (miRNAs) play crucial roles in complex cellular networks by binding to the messenger RN... more MicroRNAs (miRNAs) play crucial roles in complex cellular networks by binding to the messenger RNAs (mRNAs) of protein coding genes. It has been found that miRNA regulation is often condition-specific. A number of computational approaches have been developed to identify miRNA activity specific to a condition of interest using gene expression data. However, most of the methods only use the data in a single condition, and thus, the activity discovered may not be unique to the condition of interest. Additionally, these methods are based on statistical associations between the gene expression levels of miRNAs and mRNAs, so they may not be able to reveal real gene regulatory relationships, which are causal relationships. We propose a novel method to infer condition-specific miRNA activity by considering (i) the difference between the regulatory behavior that an miRNA has in the condition of interest and its behavior in the other conditions; (ii) the causal semantics of miRNA-mRNA relatio...

Identifying direct miRNA–mRNA causal regulatory relationships in heterogeneous data

by Thuc Le and Jiuyong Li

Journal of Biomedical Informatics, 2014

Discovering the regulatory relationships between microRNAs (miRNAs) and mRNAs is an important pro... more Discovering the regulatory relationships between microRNAs (miRNAs) and mRNAs is an important problem that interests many biologists and medical researchers. A number of computational methods have been proposed to infer miRNA-mRNA regulatory relationships, and are mostly based on the statistical associations between miRNAs and mRNAs discovered in observational data. The miRNA-mRNA regulatory relationships identified by these methods can be both direct and indirect regulations. However, differentiating direct regulatory relationships from indirect ones is important for biologists in experimental designs. In this paper, we present a causal discovery based framework (called DirectTarget) to infer direct miRNA-mRNA causal regulatory relationships in heterogeneous data, including expression profiles of miRNAs and mRNAs, and miRNA target information. DirectTarget is applied to the Epithelial to Mesenchymal Transition (EMT) datasets. The validation by experimentally confirmed target databases suggests that the proposed method can effectively identify direct miRNA-mRNA regulatory relationships. To explore the upstream regulators of miRNA regulation, we further identify the causal feedforward patterns (CFFPs) of TF-miRNA-mRNA to provide insights into the miRNA regulation in EMT. DirectTarget has the potential to be applied to other datasets to elucidate the direct miRNA-mRNA causal regulatory relationships and to explore the regulatory patterns.

A Local Causal Discovery Algorithm for High Dimensional Data

SpringerBriefs in Electrical and Computer Engineering, 2015

Causal Rule Discovery with Partial Association Test

by Thuc Le and Jiuyong Li

SpringerBriefs in Electrical and Computer Engineering, 2015

Causal Rule Discovery with Cohort Studies

SpringerBriefs in Electrical and Computer Engineering, 2015

Experimental Comparison and Discussions

by Thuc Le and Jiuyong Li

SpringerBriefs in Electrical and Computer Engineering, 2015

A fast PC algorithm for high dimensional causal discovery with multi-core PCs

by Thuc Le and Jiuyong Li

Discovering causal relationships from observational data is a crucial problem and it has applicat... more Discovering causal relationships from observational data is a crucial problem and it has applications in many research areas. The PC algorithm is the state-of-the-art constraint based method for causal discovery. However, runtime of the PC algorithm, in the worst-case, is exponential to the number of nodes (variables), and thus it is inefficient when being applied to high dimensional data, e.g. gene expression datasets. On another note, the advancement of computer hardware in the last decade has resulted in the widespread availability of multi-core personal computers. There is a significant motivation for designing a parallelised PC algorithm that is suitable for personal computers and does not require end users&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; parallel computing knowledge beyond their competency in using the PC algorithm. In this paper, we develop parallel-PC, a fast and memory efficient PC algorithm using the parallel computing technique. We apply our method to a range of synthetic and real-world high dimensional datasets. Experimental results on a dataset from the DREAM 5 challenge show that the original PC algorithm could not produce any results after running more than 24 hours; meanwhile, our parallel-PC algorithm managed to finish within around 12 hours with a 4-core CPU computer, and less than 6 hours with a 8-core CPU computer. Furthermore, we integrate parallel-PC into a causal inference method for inferring miRNA-mRNA regulatory relationships. The experimental results show that parallel-PC helps improve both the efficiency and accuracy of the causal inference algorithm.

Discovery of Causal Rules Using Partial Association

by Thuc Le and Jiuyong Li

2012 IEEE 12th International Conference on Data Mining, 2012

ABSTRACT Discovering causal relationships in large databases of observational data is challenging... more ABSTRACT Discovering causal relationships in large databases of observational data is challenging. The pioneering work in this area was rooted in the theory of Bayesian network (BN) learning, which however, is a NP-complete problem. Hence several constraint-based algorithms have been developed to efficiently discover causations in large databases. These methods usually use the idea of BN learning, directly or indirectly, and are focused on causal relationships with single cause variables. In this paper, we propose an approach to mine causal rules in large databases of binary variables. Our method expands the scope of causality discovery to causal relationships with multiple cause variables, and we utilise partial association tests to exclude noncausal associations, to ensure the high reliability of discovered causal rules. Furthermore an efficient algorithm is designed for the tests in large databases. We assess the method with a set of real-world diagnostic data. The results show that our method can effectively discover interesting causal rules in large databases.

Mining Causal Association Rules

2013 IEEE 13th International Conference on Data Mining Workshops, 2013

ABSTRACT Discovering causal relationships is the ultimate goal of many scientific explorations. C... more ABSTRACT Discovering causal relationships is the ultimate goal of many scientific explorations. Causal relationships can be identified with controlled experiments, but such experiments are often very expensive and sometimes impossible to conduct. On the other hand, the collection of observational data has increased dramatically in recent decades. Therefore it is desirable to find causal relationships from the data directly. Significant progress has been made in the field of discovering causal relationships using the Causal Bayesian Network (CBN) theory. The applications of CBNs, however, are greatly limited due to the high computational complexity. In another direction, association rule mining has been shown to be an efficient data mining means for relationship discovery. However, although causal relationships imply associations, the reverse does not always hold. In this paper we study how to use an efficient association mining approach to discover potential causal rules in observational data. We make use of the idea of retrospective cohort studies, a widely used approach in medical and social research, to detect causal association rules. In comparison with the constraint-based methods within the CBN paradigm, the proposed approach is faster and is capable of finding a cause consisting of combined variables.