scholarly journals Rationalizing Translation Elongation by Reinforcement Learning

2018 ◽  
Author(s):  
Hailin Hu ◽  
Xianggen Liu ◽  
An Xiao ◽  
Sen Song ◽  
Jianyang Zeng

AbstractTranslation elongation plays a crucial role in multiple aspects of protein biogenesis. In this study, we develop a novel deep reinforcement learning based framework, named RiboRL, to model the distributions of ribosomes on transcripts. In particular, RiboRL employs a policy network (PolicyNet) to perform a context-dependent feature selection to facilitate the prediction of ribosome density. Extensive tests demonstrate that RiboRL can outperform other state-of-the-art methods in predicting ribosome densities. We also show that the reinforcement learning based strategy can generate more informative features for the prediction task when compared to other commonly used attribution methods in deep learning. Moreover, the in-depth analyses and a case study also indicate the potential applications of the RiboRL framework in generating meaningful biological insights regarding translation elongation dynamics. These results have established RiboRL as a useful computational tool to facilitate the studies of the underlying mechanisms of translational regulation.

2019 ◽  
Author(s):  
Pedro do Couto Bordignon ◽  
Sebastian Pechmann

Translation of messenger RNAs into proteins by the ribosome is the most important step of protein biosynthesis. Accordingly, translation is tightly controlled and heavily regulated to maintain cellular homeostasis. Ribosome profiling (Ribo-seq) has revolutionized the study of translation by revealing many of its underlying mechanisms. However, equally many aspects of translation remain mysterious, in part also due to persisting challenges in the interpretation of data obtained from Ribo-seq experiments. Here, we show that some of the variability observed in Ribo-seq data has biological origins and reflects programmed heterogeneity of translation. To systematically identify sequences that are differentially translated (DT) across mRNAs beyond what can be attributed to experimental variability, we performed a comparative analysis of Ribo-seq data from Saccharomyces cerevisiae and derived a consensus ribosome density profile that reflects consistent signals in individual experiments. Remarkably, the thus identified DT sequences link to mechanisms known to regulate translation elongation and are enriched in genes important for protein and organelle biosynthesis. Our results thus highlight examples of translational heterogeneity that are encoded in the genomic sequences and tuned to optimizing cellular homeostasis. More generally, our work highlights the power of Ribo-seq to understand the complexities of translation regulation.


Author(s):  
Penghui Wei ◽  
Wenji Mao ◽  
Guandan Chen

Analyzing public attitudes plays an important role in opinion mining systems. Stance detection aims to determine from a text whether its author is in favor of, against, or neutral towards a given target. One challenge of this task is that a text may not explicitly express an attitude towards the target, but existing approaches utilize target content alone to build models. Moreover, although weakly supervised approaches have been proposed to ease the burden of manually annotating largescale training data, such approaches are confronted with noisy labeling problem. To address the above two issues, in this paper, we propose a Topic-Aware Reinforced Model (TARM) for weakly supervised stance detection. Our model consists of two complementary components: (1) a detection network that incorporates target-related topic information into representation learning for identifying stance effectively; (2) a policy network that learns to eliminate noisy instances from auto-labeled data based on off-policy reinforcement learning. Two networks are alternately optimized to improve each other’s performances. Experimental results demonstrate that our proposed model TARM outperforms the state-of-the-art approaches.


Author(s):  
Sven Gronauer ◽  
Martin Gottwald ◽  
Klaus Diepold

Despite the sublime success in recent years, the underlying mechanisms powering the advances of reinforcement learning are yet poorly understood. In this paper, we identify these mechanisms - which we call ingredients - in on-policy policy gradient methods and empirically determine their impact on the learning. To allow an equitable assessment, we conduct our experiments based on a unified and modular implementation. Our results underline the significance of recent algorithmic advances and demonstrate that reaching state-of-the-art performance may not need sophisticated algorithms but can also be accomplished by the combination of a few simple ingredients.


Author(s):  
Ryuichi Takanobu ◽  
Minlie Huang ◽  
Zhongzhou Zhao ◽  
Fenglin Li ◽  
Haiqing Chen ◽  
...  

Topic structure analysis plays a pivotal role in dialogue understanding. We propose a reinforcement learning (RL) method for topic segmentation and labeling in goal-oriented dialogues, which aims to detect topic boundaries among dialogue utterances and assign topic labels to the utterances. We address three common issues in the goal-oriented customer service dialogues: informality, local topic continuity, and global topic structure. We explore the task in a weakly supervised setting and formulate it as a sequential decision problem. The proposed method consists of a state representation network to address the informality issue, and a policy network with rewards to model local topic continuity and global topic structure. To train the two networks and offer a warm-start to the policy, we firstly use some keywords to annotate the data automatically. We then pre-train the networks on noisy data. Henceforth, the method continues to refine the data labels using the current policy to learn better state representations on the refined data for obtaining a better policy. Results demonstrate that this weakly supervised method obtains substantial improvements over state-of-the-art baselines.


2019 ◽  
Author(s):  
Niclas Ståhl ◽  
Göran Falkman ◽  
Alexander Karlsson ◽  
Gunnar Mathiason ◽  
Jonas Boström

<p>In medicinal chemistry programs it is key to design and make compounds that are efficacious and safe. This is a long, complex and difficult multi-parameter optimization process, often including several properties with orthogonal trends. New methods for the automated design of compounds against profiles of multiple properties are thus of great value. Here we present a fragment-based reinforcement learning approach based on an actor-critic model, for the generation of novel molecules with optimal properties. The actor and the critic are both modelled with bidirectional long short-term memory (LSTM) networks. The AI method learns how to generate new compounds with desired properties by starting from an initial set of lead molecules and then improve these by replacing some of their fragments. A balanced binary tree based on the similarity of fragments is used in the generative process to bias the output towards structurally similar molecules. The method is demonstrated by a case study showing that 93% of the generated molecules are chemically valid, and a third satisfy the targeted objectives, while there were none in the initial set.</p>


Author(s):  
Ginestra Bianconi

Defining the centrality of nodes and layers in multilayer networks is of fundamental importance for a variety of applications from sociology to biology and finance. This chapter presents the state-of-the-art centrality measures able to characterize the centrality of nodes, the influences of layers or the centrality of replica nodes in multilayer and multiplex networks. These centrality measures include modifications of the eigenvector centrality, Katz centrality, PageRank centrality and Communicability to the multilayer network scenario. The chapter provides a comprehensive description of the research of the field and discusses the main advantages and limitations of the different definitions, allowing the readers that wish to apply these techniques to choose the most suitable definition for his or her case study.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yangfan Xu ◽  
Xianqun Fan ◽  
Yang Hu

AbstractEnzyme-catalyzed proximity labeling (PL) combined with mass spectrometry (MS) has emerged as a revolutionary approach to reveal the protein-protein interaction networks, dissect complex biological processes, and characterize the subcellular proteome in a more physiological setting than before. The enzymatic tags are being upgraded to improve temporal and spatial resolution and obtain faster catalytic dynamics and higher catalytic efficiency. In vivo application of PL integrated with other state of the art techniques has recently been adapted in live animals and plants, allowing questions to be addressed that were previously inaccessible. It is timely to summarize the current state of PL-dependent interactome studies and their potential applications. We will focus on in vivo uses of newer versions of PL and highlight critical considerations for successful in vivo PL experiments that will provide novel insights into the protein interactome in the context of human diseases.


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