Easing Embedding Learning by Comprehensive Transcription of Heterogeneous Information Networks

Heterogeneous information networks (HINs) are ubiquitous in real-world applications. In the meantime, network embedding has emerged as a convenient tool to mine and learn from networked data. As a result, it is of interest to develop HIN embedding methods. However, the heterogeneity in HINs introduces not only rich information but also potentially incompatible semantics, which poses special challenges to embedding learning in HINs. With the intention to preserve the rich yet potentially incompatible information in HIN embedding, we propose to study the problem of comprehensive transcription of heterogeneous information networks. The comprehensive transcription of HINs also provides an easy-to-use approach to unleash the power of HINs, since it requires no additional supervision, expertise, or feature engineering. To cope with the challenges in the comprehensive transcription of HINs, we propose the HEER algorithm, which embeds HINs via edge representations that are further coupled with properly-learned heterogeneous metrics. To corroborate the efficacy of HEER, we conducted experiments on two large-scale real-words datasets with an edge reconstruction task and multiple case studies. Experiment results demonstrate the effectiveness of the proposed HEER model and the utility of edge representations and heterogeneous metrics. The code and data are available at https://github.com/GentleZhu/HEER.Comment: 10 pages. In Proceedings of the 24th ACM SIGKDD International Conference on Knowledge Discovery and Data Mining, London, United Kingdom, ACM, 201

From data towards knowledge: Revealing the architecture of signaling systems by unifying knowledge mining and data mining of systematic perturbation data

Genetic and pharmacological perturbation experiments, such as deleting a gene and monitoring gene expression responses, are powerful tools for studying cellular signal transduction pathways. However, it remains a challenge to automatically derive knowledge of a cellular signaling system at a conceptual level from systematic perturbation-response data. In this study, we explored a framework that unifies knowledge mining and data mining approaches towards the goal. The framework consists of the following automated processes: 1) applying an ontology-driven knowledge mining approach to identify functional modules among the genes responding to a perturbation in order to reveal potential signals affected by the perturbation; 2) applying a graph-based data mining approach to search for perturbations that affect a common signal with respect to a functional module, and 3) revealing the architecture of a signaling system organize signaling units into a hierarchy based on their relationships. Applying this framework to a compendium of yeast perturbation-response data, we have successfully recovered many well-known signal transduction pathways; in addition, our analysis have led to many hypotheses regarding the yeast signal transduction system; finally, our analysis automatically organized perturbed genes as a graph reflecting the architect of the yeast signaling system. Importantly, this framework transformed molecular findings from a gene level to a conceptual level, which readily can be translated into computable knowledge in the form of rules regarding the yeast signaling system, such as "if genes involved in MAPK signaling are perturbed, genes involved in pheromone responses will be differentially expressed"

Community detection in directed acyclic graphs

Some temporal networks, most notably citation networks, are naturally represented as directed acyclic graphs (DAGs). To detect communities in DAGs, we propose a modularity for DAGs by defining an appropriate null model (i.e., randomized network) respecting the order of nodes. We implement a spectral method to approximately maximize the proposed modularity measure and test the method on citation networks and other DAGs. We find that the attained values of the modularity for DAGs are similar for partitions that we obtain by maximizing the proposed modularity (designed for DAGs), the modularity for undirected networks and that for general directed networks. In other words, if we neglect the order imposed on nodes (and the direction of links) in a given DAG and maximize the conventional modularity measure, the obtained partition is close to the optimal one in the sense of the modularity for DAGs.Comment: 2 figures, 7 table

The potential of text mining in data integration and network biology for plant research : a case study on Arabidopsis

Despite the availability of various data repositories for plant research, a wealth of information currently remains hidden within the biomolecular literature. Text mining provides the necessary means to retrieve these data through automated processing of texts. However, only recently has advanced text mining methodology been implemented with sufficient computational power to process texts at a large scale. In this study, we assess the potential of large-scale text mining for plant biology research in general and for network biology in particular using a state-of-the-art text mining system applied to all PubMed abstracts and PubMed Central full texts. We present extensive evaluation of the textual data for Arabidopsis thaliana, assessing the overall accuracy of this new resource for usage in plant network analyses. Furthermore, we combine text mining information with both protein-protein and regulatory interactions from experimental databases. Clusters of tightly connected genes are delineated from the resulting network, illustrating how such an integrative approach is essential to grasp the current knowledge available for Arabidopsis and to uncover gene information through guilt by association. All large-scale data sets, as well as the manually curated textual data, are made publicly available, hereby stimulating the application of text mining data in future plant biology studies

Discovering Graphical Granger Causality Using the Truncating Lasso Penalty

Components of biological systems interact with each other in order to carry out vital cell functions. Such information can be used to improve estimation and inference, and to obtain better insights into the underlying cellular mechanisms. Discovering regulatory interactions among genes is therefore an important problem in systems biology. Whole-genome expression data over time provides an opportunity to determine how the expression levels of genes are affected by changes in transcription levels of other genes, and can therefore be used to discover regulatory interactions among genes. In this paper, we propose a novel penalization method, called truncating lasso, for estimation of causal relationships from time-course gene expression data. The proposed penalty can correctly determine the order of the underlying time series, and improves the performance of the lasso-type estimators. Moreover, the resulting estimate provides information on the time lag between activation of transcription factors and their effects on regulated genes. We provide an efficient algorithm for estimation of model parameters, and show that the proposed method can consistently discover causal relationships in the large $p$, small $n$ setting. The performance of the proposed model is evaluated favorably in simulated, as well as real, data examples. The proposed truncating lasso method is implemented in the R-package grangerTlasso and is available at http://www.stat.lsa.umich.edu/~shojaie.Comment: 12 pages, 4 figures, 1 tabl

Modelling epistasis in genetic disease using Petri nets, evolutionary computation and frequent itemset mining

Petri nets are useful for mathematically modelling disease-causing genetic epistasis. A Petri net model of an interaction has the potential to lead to biological insight into the cause of a genetic disease. However, defining a Petri net by hand for a particular interaction is extremely difficult because of the sheer complexity of the problem and degrees of freedom inherent in a Petri net’s architecture. We propose therefore a novel method, based on evolutionary computation and data mining, for automatically constructing Petri net models of non-linear gene interactions. The method comprises two main steps. Firstly, an initial partial Petri net is set up with several repeated sub-nets that model individual genes and a set of constraints, comprising relevant common sense and biological knowledge, is also defined. These constraints characterise the class of Petri nets that are desired. Secondly, this initial Petri net structure and the constraints are used as the input to a genetic algorithm. The genetic algorithm searches for a Petri net architecture that is both a superset of the initial net, and also conforms to all of the given constraints. The genetic algorithm evaluation function that we employ gives equal weighting to both the accuracy of the net and also its parsimony. We demonstrate our method using an epistatic model related to the presence of digital ulcers in systemic sclerosis patients that was recently reported in the literature. Our results show that although individual “perfect” Petri nets can frequently be discovered for this interaction, the true value of this approach lies in generating many different perfect nets, and applying data mining techniques to them in order to elucidate common and statistically significant patterns of interaction

Inherent size constraints on prokaryote gene networks due to "accelerating" growth

Networks exhibiting "accelerating" growth have total link numbers growing faster than linearly with network size and can exhibit transitions from stationary to nonstationary statistics and from random to scale-free to regular statistics at particular critical network sizes. However, if for any reason the network cannot tolerate such gross structural changes then accelerating networks are constrained to have sizes below some critical value. This is of interest as the regulatory gene networks of single celled prokaryotes are characterized by an accelerating quadratic growth and are size constrained to be less than about 10,000 genes encoded in DNA sequence of less than about 10 megabases. This paper presents a probabilistic accelerating network model for prokaryotic gene regulation which closely matches observed statistics by employing two classes of network nodes (regulatory and non-regulatory) and directed links whose inbound heads are exponentially distributed over all nodes and whose outbound tails are preferentially attached to regulatory nodes and described by a scale free distribution. This model explains the observed quadratic growth in regulator number with gene number and predicts an upper prokaryote size limit closely approximating the observed value.Comment: Corrected error in biological input parameter: 15 pages, 10 figure