BackgroundIn cell differentiation, a cell of a less specialized type becomes one of a more specialized type, even though all cells have the same genome. Transcription factors and epigenetic marks like histone modifications can play a significant role in the differentiation process.ResultsIn this paper, we present a simple analysis of cell types and differentiation paths using phylogenetic inference based on ChIP-Seq histone modification data. We precisely defined the notion of cell-type trees and provided a procedure of building such trees. We propose new data representation techniques and distance measures for ChIP-Seq data and use these together with standard phylogenetic inference methods to build biologically meaningful cell-type trees that indicate how diverse types of cells are related. We demonstrate our approach on various kinds of histone modifications for various cell types, also using the datasets to explore various issues surrounding replicate data, variability between cells of the same type, and robustness. We use the results to get some interesting biological findings like important patterns of histone modification changes during cell differentiation process.ConclusionsWe introduced and studied the novel problem of inferring cell type trees from histone modification data. The promising results we obtain point the way to a new approach to the study of cell differentiation. We also discuss how cell-type trees can be used to study the evolution of cell types.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2105-15-269) contains supplementary material, which is available to authorized users.
We consider the problem of training generative models with a Generative Adversarial Network (GAN). Although GANs can accurately model complex distributions, they are known to be difficult to train due to instabilities caused by a difficult minimax optimization problem. In this paper, we view the problem of training GANs as finding a mixed strategy in a zero-sum game. Building on ideas from online learning we propose a novel training method named Chekhov GAN 1 . On the theory side, we show that our method provably converges to an equilibrium for semi-shallow GAN architectures, i.e. architectures where the discriminator is a one layer network and the generator is arbitrary. On the practical side, we develop an efficient heuristic guided by our theoretical results, which we apply to commonly used deep GAN architectures. On several real world tasks our approach exhibits improved stability and performance compared to standard GAN training.
We explore neural network models for answering multi-step reasoning questions that operate on semi-structured tables. Challenges arise from deep logical compositionality and domain openness. Our approach is weakly supervised, trained on question-answer-table triples. It generates human readable logical forms from natural language questions, which are then ranked based on word and character convolutional neural networks. A model ensemble achieved at the moment of publication state-of-the-art score on the WikiTableQuestions dataset.
BackgroundIn cell differentiation, a less specialized cell differentiates into a more specialized one, even though all cells in one organism have (almost) the same genome. Epigenetic factors such as histone modifications are known to play a significant role in cell differentiation. We previously introduce cell-type trees to represent the differentiation of cells into more specialized types, a representation that partakes of both ontogeny and phylogeny.ResultsWe propose a maximum-likelihood (ML) approach to build cell-type trees and show that this ML approach outperforms our earlier distance-based and parsimony-based approaches. We then study the reconstruction of ancestral cell types; since both ancestral and derived cell types can coexist in adult organisms, we propose a lifting algorithm to infer internal nodes. We present results on our lifting algorithm obtained both through simulations and on real datasets.ConclusionsWe show that our ML-based approach outperforms previously proposed techniques such as distance-based and parsimony-based methods. We show our lifting-based approach works well on both simulated and real data.
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