scholarly journals BARcode DEmixing through Non-negative Spatial Regression (BarDensr)

2020 ◽  
Author(s):  
Shuonan Chen ◽  
Jackson Loper ◽  
Xiaoyin Chen ◽  
Tony Zador ◽  
Liam Paninski
Keyword(s):  
Convex Optimization ◽  
Spatial Resolution ◽  
Spatial Regression ◽  
Real Data ◽  
Computational Method ◽  
Spatial Density ◽  
Signal Recovery ◽  
Optimization Approach ◽  
Imaging Data ◽  
Imaging Resolution

AbstractModern spatial transcriptomics methods can target thousands of different types of RNA transcripts in a single slice of tissue. Many biological applications demand a high spatial density of transcripts relative to the imaging resolution, leading to partial mixing of transcript rolonies in many pixels; unfortunately, current analysis methods do not perform robustly in this highly-mixed setting. Here we develop a new analysis approach, BARcode DEmixing through Non-negative Spatial Regression (BarDensr): we start with a generative model of the physical process that leads to the observed image data and then apply sparse convex optimization methods to estimate the underlying (demixed) rolony densities. We apply Bar-Densr to simulated and real data and find that it achieves state of the art signal recovery, particularly in densely-labeled regions or data with low spatial resolution. Finally, BarDensr is fast and parallelizable. We provide open-source code as well as an implementation for the ‘NeuroCAAS’ cloud platform.Author SummarySpatial transcriptomics technologies allow us to simultaneously detect multiple molecular targets in the context of intact tissues. These experiments yield images that answer two questions: which kinds of molecules are present, and where are they located in the tissue? In many experiments (e.g., mapping RNA expression in fine neuronal processes), it is desirable to increase the signal density relative to the imaging resolution. This may lead to mixing of signals from multiple RNA molecules into single imaging pixels; thus we need to demix the signals from these images. Here we introduce BarDensr, a new computational method to perform this demixing. The method is based on a forward model of the imaging process, followed by a convex optimization approach to approximately ‘invert’ mixing induced during imaging. This new approach leads to significantly improved performance in demixing imaging data with dense expression and/or low spatial resolution.

scholarly journals BARcode DEmixing through Non-negative Spatial Regression (BarDensr)

2021 ◽  
Vol 17 (3) ◽  
pp. e1008256
Author(s):  
Shuonan Chen ◽  
Jackson Loper ◽  
Xiaoyin Chen ◽  
Alex Vaughan ◽  
Anthony M. Zador ◽  
...  
Keyword(s):  
State Of The Art ◽  
Spatial Regression ◽  
Image Data ◽  
Real Data ◽  
Optimization Methods ◽  
Spatial Density ◽  
Signal Recovery ◽  
Cloud Platform ◽  
Rna Transcripts ◽  
Different Types

Modern spatial transcriptomics methods can target thousands of different types of RNA transcripts in a single slice of tissue. Many biological applications demand a high spatial density of transcripts relative to the imaging resolution, leading to partial mixing of transcript rolonies in many voxels; unfortunately, current analysis methods do not perform robustly in this highly-mixed setting. Here we develop a new analysis approach, BARcode DEmixing through Non-negative Spatial Regression (BarDensr): we start with a generative model of the physical process that leads to the observed image data and then apply sparse convex optimization methods to estimate the underlying (demixed) rolony densities. We apply BarDensr to simulated and real data and find that it achieves state of the art signal recovery, particularly in densely-labeled regions or data with low spatial resolution. Finally, BarDensr is fast and parallelizable. We provide open-source code as well as an implementation for the ‘NeuroCAAS’ cloud platform.

scholarly journals Maximizing protein translation rate in the non-homogeneous ribosome flow model: a convex optimization approach

2014 ◽  
Vol 11 (100) ◽  
pp. 20140713 ◽  
Author(s):  
Gilad Poker ◽  
Yoram Zarai ◽  
Michael Margaliot ◽  
Tamir Tuller
Keyword(s):  
Synthetic Biology ◽  
Convex Optimization ◽  
Production Rate ◽  
Protein Production ◽  
Flow Model ◽  
Protein Translation ◽  
Optimization Approach ◽  
Initiation Rate ◽  
Translation Rate ◽  
Protein Production Rate

Translation is an important stage in gene expression. During this stage, macro-molecules called ribosomes travel along the mRNA strand linking amino acids together in a specific order to create a functioning protein. An important question, related to many biomedical disciplines, is how to maximize protein production. Indeed, translation is known to be one of the most energy-consuming processes in the cell, and it is natural to assume that evolution shaped this process so that it maximizes the protein production rate. If this is indeed so then one can estimate various parameters of the translation machinery by solving an appropriate mathematical optimization problem. The same problem also arises in the context of synthetic biology, namely, re-engineer heterologous genes in order to maximize their translation rate in a host organism. We consider the problem of maximizing the protein production rate using a computational model for translation–elongation called the ribosome flow model (RFM). This model describes the flow of the ribosomes along an mRNA chain of length n using a set of n first-order nonlinear ordinary differential equations. It also includes n + 1 positive parameters: the ribosomal initiation rate into the mRNA chain, and n elongation rates along the chain sites. We show that the steady-state translation rate in the RFM is a strictly concave function of its parameters. This means that the problem of maximizing the translation rate under a suitable constraint always admits a unique solution, and that this solution can be determined using highly efficient algorithms for solving convex optimization problems even for large values of n . Furthermore, our analysis shows that the optimal translation rate can be computed based only on the optimal initiation rate and the elongation rate of the codons near the beginning of the ORF. We discuss some applications of the theoretical results to synthetic biology, molecular evolution, and functional genomics.

scholarly journals Trivariate Empirical Mode Decomposition via Convex Optimization for Rolling Bearing Condition Identification

Sensors ◽  
2018 ◽  
Vol 18 (7) ◽  
pp. 2325 ◽  
Author(s):  
Yong Lv ◽  
Houzhuang Zhang ◽  
Cancan Yi
Keyword(s):  
Convex Optimization ◽  
Empirical Mode Decomposition ◽  
Dimensional Space ◽  
Real Data ◽  
Rolling Bearing ◽  
Low Rank ◽  
Data Matrix ◽  
Mode Decomposition ◽  
Uniform Sample ◽  
Local Mean

As a multichannel signal processing method based on data-driven, multivariate empirical mode decomposition (MEMD) has attracted much attention due to its potential ability in self-adaption and multi-scale decomposition for multivariate data. Commonly, the uniform projection scheme on a hypersphere is used to estimate the local mean. However, the unbalanced data distribution in high-dimensional space often conflicts with the uniform samples and its performance is sensitive to the noise components. Considering the common fact that the vibration signal is generated by three sensors located in different measuring positions in the domain of the structural health monitoring for the key equipment, thus a novel trivariate empirical mode decomposition via convex optimization was proposed for rolling bearing condition identification in this paper. For the trivariate data matrix, the low-rank matrix approximation via convex optimization was firstly conducted to achieve the denoising. It is worthy to note that the non-convex penalty function as a regularization term is introduced to enhance the performance. Moreover, the non-uniform sample scheme was determined by applying singular value decomposition (SVD) to the obtained low-rank trivariate data and then the approach used in conventional MEMD algorithm was employed to estimate the local mean. Numerical examples of synthetic defined by the fault model and real data generated by the fault rolling bearing on the experimental bench are provided to demonstrate the fruitful applications of the proposed method.

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