Missing value imputation for epistatic MAPs

<p>Abstract</p> <p>Background</p> <p>Epistatic miniarray profiling (E-MAPs) is a high-throughput approach capable of quantifying aggravating or alleviating genetic interactions between gene pairs. The datasets resulting from E-MAP experiments typically take the form of a symmetric pairwise matrix of interaction scores. These datasets have a significant number of missing values - up to 35% - that can reduce the effectiveness of some data analysis techniques and prevent the use of others. An effective method for imputing interactions would therefore increase the types of possible analysis, as well as increase the potential to identify novel functional interactions between gene pairs. Several methods have been developed to handle missing values in microarray data, but it is unclear how applicable these methods are to E-MAP data because of their pairwise nature and the significantly larger number of missing values. Here we evaluate four alternative imputation strategies, three local (Nearest neighbor-based) and one global (PCA-based), that have been modified to work with symmetric pairwise data.</p> <p>Results</p> <p>We identify different categories for the missing data based on their underlying cause, and show that values from the largest category can be imputed effectively. We compare local and global imputation approaches across a variety of distinct E-MAP datasets, showing that both are competitive and preferable to filling in with zeros. In addition we show that these methods are effective in an E-MAP from a different species, suggesting that pairwise imputation techniques will be increasingly useful as analogous epistasis mapping techniques are developed in different species. We show that strongly alleviating interactions are significantly more difficult to predict than strongly aggravating interactions. Finally we show that imputed interactions, generated using nearest neighbor methods, are enriched for annotations in the same manner as measured interactions. Therefore our method potentially expands the number of mapped epistatic interactions. In addition we make implementations of our algorithms available for use by other researchers.</p> <p>Conclusions</p> <p>We address the problem of missing value imputation for E-MAPs, and suggest the use of symmetric nearest neighbor based approaches as they offer consistently accurate imputations across multiple datasets in a tractable manner.</p

Deep generative modeling for single-cell transcriptomics.

Single-cell transcriptome measurements can reveal unexplored biological diversity, but they suffer from technical noise and bias that must be modeled to account for the resulting uncertainty in downstream analyses. Here we introduce single-cell variational inference (scVI), a ready-to-use scalable framework for the probabilistic representation and analysis of gene expression in single cells ( https://github.com/YosefLab/scVI ). scVI uses stochastic optimization and deep neural networks to aggregate information across similar cells and genes and to approximate the distributions that underlie observed expression values, while accounting for batch effects and limited sensitivity. We used scVI for a range of fundamental analysis tasks including batch correction, visualization, clustering, and differential expression, and achieved high accuracy for each task

Enhancing Domain Word Embedding via Latent Semantic Imputation

We present a novel method named Latent Semantic Imputation (LSI) to transfer external knowledge into semantic space for enhancing word embedding. The method integrates graph theory to extract the latent manifold structure of the entities in the affinity space and leverages non-negative least squares with standard simplex constraints and power iteration method to derive spectral embeddings. It provides an effective and efficient approach to combining entity representations defined in different Euclidean spaces. Specifically, our approach generates and imputes reliable embedding vectors for low-frequency words in the semantic space and benefits downstream language tasks that depend on word embedding. We conduct comprehensive experiments on a carefully designed classification problem and language modeling and demonstrate the superiority of the enhanced embedding via LSI over several well-known benchmark embeddings. We also confirm the consistency of the results under different parameter settings of our method.Comment: ACM SIGKDD 201

Anomaly detection in unknown environments using wireless sensor networks

This dissertation addresses the problem of distributed anomaly detection in Wireless Sensor Networks (WSN). A challenge of designing such systems is that the sensor nodes are battery powered, often have different capabilities and generally operate in dynamic environments. Programming such sensor nodes at a large scale can be a tedious job if the system is not carefully designed. Data modeling in distributed systems is important for determining the normal operation mode of the system. Being able to model the expected sensor signatures for typical operations greatly simplifies the human designer’s job by enabling the system to autonomously characterize the expected sensor data streams. This, in turn, allows the system to perform autonomous anomaly detection to recognize when unexpected sensor signals are detected. This type of distributed sensor modeling can be used in a wide variety of sensor networks, such as detecting the presence of intruders, detecting sensor failures, and so forth. The advantage of this approach is that the human designer does not have to characterize the anomalous signatures in advance. The contributions of this approach include: (1) providing a way for a WSN to autonomously model sensor data with no prior knowledge of the environment; (2) enabling a distributed system to detect anomalies in both sensor signals and temporal events online; (3) providing a way to automatically extract semantic labels from temporal sequences; (4) providing a way for WSNs to save communication power by transmitting compressed temporal sequences; (5) enabling the system to detect time-related anomalies without prior knowledge of abnormal events; and, (6) providing a novel missing data estimation method that utilizes temporal and spatial information to replace missing values. The algorithms have been designed, developed, evaluated, and validated experimentally in synthesized data, and in real-world sensor network applications