Infinia ML (United States)

Identifying meaningful cancer driver genes in a cohort of tumors is a challenging task in cancer genomics. Although existing studies have identified known cancer drivers, most of them focus on detecting coding drivers with mutations. It is acknowledged that non-coding drivers can regulate driver mutations to promote cancer growth. In this work, we propose a novel node importance-based network analysis (NIBNA) framework to detect coding and non-coding cancer drivers. We hypothesize that cancer drivers are crucial to the formation of community structures in cancer network, and removing them from the network greatly perturbs the network structure thereby critically affecting the functioning of the network. NIBNA detects cancer drivers using a three-step process: first, a condition-specific network is built by incorporating gene expression data and gene networks; second, the community structures in the network are estimated; and third, a centrality-based metric is applied to compute node importance. We apply NIBNA to the BRCA dataset, and it outperforms existing state-of-art methods in detecting coding cancer drivers. NIBNA also predicts 265 miRNA drivers, and majority of these drivers have been validated in literature. Further we apply NIBNA to detect cancer subtype-specific drivers, and several predicted drivers have been validated to be associated with cancer subtypes. Lastly, we evaluate NIBNA's performance in detecting epithelial-mesenchymal transition drivers, and we confirmed 8 coding and 13 miRNA drivers in the list of known genes. The source code can be accessed at https://github.com/mandarsc/NIBNA. Supplementary data are available at Bioinformatics online.

Abstract When galaxies merge, the supermassive black holes in their centers may form binaries and emit low-frequency gravitational radiation in the process. In this paper, we consider the galaxy 3C 66B, which was used as the target of the first multimessenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational-wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C 66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C 66B to less than (1.65 ± 0.02) × 109 M ⊙ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data over “blind” pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.

Real-world entities' behaviors, associated with their side information, are often recorded over time as asynchronous event sequences. Such event sequences are the basis of many practical applications, neural spiking train study, earth quack prediction, crime analysis, infectious disease diffusion forecasting, condition-based preventative maintenance, information retrieval and behavior-based network analysis and services, etc. Temporal point process (TPP) is a principled mathematical tool for the modeling and learning of asynchronous event sequences, which captures the instantaneous happening rate of the events and the temporal dependency between historical and current events. TPP provides us with an interpretable model to describe the generative mechanism of event sequences, which is beneficial for event prediction and causality analysis. Recently, it has been shown that TPP has potentials to many machine learning and data science applications and can be combined with other cutting-edge machine learning techniques like deep learning, reinforcement learning, adversarial learning, and so on. We will start with an elementary introduction of TPP model, including the basic concepts of the model, the simulation method of event sequences; in the second part of the tutorial, we will introduce typical TPP models and their traditional learning methods; in the third part of the tutorial, we will discuss the recent progress on the modeling and learning of TPP, including neural network-based TPP models, generative adversarial networks (GANs) for TPP, and deep reinforcement learning of TPP. We will further talk about the practical application of TPP, including useful data augmentation methods for learning from imperfect observations, typical applications and examples like healthcare and industry maintenance, and existing open source toolboxes.