Transcription Factor-DNA Binding Via Machine Learning Ensembles

We present ensemble methods in a machine learning (ML) framework combining predictions from five known motif/binding site exploration algorithms. For a given TF the ensemble starts with position weight matrices (PWM's) for the motif, collected from the component algorithms. Using dimension reduction, we identify significant PWM-based subspaces for analysis. Within each subspace a machine classifier is built for identifying the TF's gene (promoter) targets (Problem 1). These PWM-based subspaces form an ML-based sequence analysis tool. Problem 2 (finding binding motifs) is solved by agglomerating k-mer (string) feature PWM-based subspaces that stand out in identifying gene targets. We approach Problem 3 (binding sites) with a novel machine learning approach that uses promoter string features and ML importance scores in a classification algorithm locating binding sites across the genome. For target gene identification this method improves performance (measured by the F1 score) by about 10 percentage points over the (a) motif scanning method and (b) the coexpression-based association method. Top motif outperformed 5 component algorithms as well as two other common algorithms (BEST and DEME). For identifying individual binding sites on a benchmark cross species database (Tompa et al., 2005) we match the best performer without much human intervention. It also improved the performance on mammalian TFs. The ensemble can integrate orthogonal information from different weak learners (potentially using entirely different types of features) into a machine learner that can perform consistently better for more TFs. The TF gene target identification component (problem 1 above) is useful in constructing a transcriptional regulatory network from known TF-target associations. The ensemble is easily extendable to include more tools as well as future PWM-based information.Comment: 33 page

Implications of Z-normalization in the matrix profile

Companies are increasingly measuring their products and services, resulting in a rising amount of available time series data, making techniques to extract usable information needed. One state-of-the-art technique for time series is the Matrix Profile, which has been used for various applications including motif/discord discovery, visualizations and semantic segmentation. Internally, the Matrix Profile utilizes the z-normalized Euclidean distance to compare the shape of subsequences between two series. However, when comparing subsequences that are relatively flat and contain noise, the resulting distance is high despite the visual similarity of these subsequences. This property violates some of the assumptions made by Matrix Profile based techniques, resulting in worse performance when series contain flat and noisy subsequences. By studying the properties of the z-normalized Euclidean distance, we derived a method to eliminate this effect requiring only an estimate of the standard deviation of the noise. In this paper we describe various practical properties of the z-normalized Euclidean distance and show how these can be used to correct the performance of Matrix Profile related techniques. We demonstrate our techniques using anomaly detection using a Yahoo! Webscope anomaly dataset, semantic segmentation on the PAMAP2 activity dataset and for data visualization on a UCI activity dataset, all containing real-world data, and obtain overall better results after applying our technique. Our technique is a straightforward extension of the distance calculation in the Matrix Profile and will benefit any derived technique dealing with time series containing flat and noisy subsequences

PATTERNA: transcriptome-wide search for functional RNA elements via structural data signatures.

Establishing a link between RNA structure and function remains a great challenge in RNA biology. The emergence of high-throughput structure profiling experiments is revolutionizing our ability to decipher structure, yet principled approaches for extracting information on structural elements directly from these data sets are lacking. We present PATTERNA, an unsupervised pattern recognition algorithm that rapidly mines RNA structure motifs from profiling data. We demonstrate that PATTERNA detects motifs with an accuracy comparable to commonly used thermodynamic models and highlight its utility in automating data-directed structure modeling from large data sets. PATTERNA is versatile and compatible with diverse profiling techniques and experimental conditions

FLEET: Butterfly Estimation from a Bipartite Graph Stream

We consider space-efficient single-pass estimation of the number of butterflies, a fundamental bipartite graph motif, from a massive bipartite graph stream where each edge represents a connection between entities in two different partitions. We present a space lower bound for any streaming algorithm that can estimate the number of butterflies accurately, as well as FLEET, a suite of algorithms for accurately estimating the number of butterflies in the graph stream. Estimates returned by the algorithms come with provable guarantees on the approximation error, and experiments show good tradeoffs between the space used and the accuracy of approximation. We also present space-efficient algorithms for estimating the number of butterflies within a sliding window of the most recent elements in the stream. While there is a significant body of work on counting subgraphs such as triangles in a unipartite graph stream, our work seems to be one of the few to tackle the case of bipartite graph streams.Comment: This is the author's version of the work. It is posted here by permission of ACM for your personal use. Not for redistribution. The definitive version was published in Seyed-Vahid Sanei-Mehri, Yu Zhang, Ahmet Erdem Sariyuce and Srikanta Tirthapura. "FLEET: Butterfly Estimation from a Bipartite Graph Stream". The 28th ACM International Conference on Information and Knowledge Managemen