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Machine learning-guided channelrhodopsin engineering enables minimally invasive optogenetics

Machine learning-guided channelrhodopsin engineering enables...

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作者： Claire N. Bedbrook Kevin K. Yang J. Elliott Robinson Elisha D. Mackey Viviana Gradinaru Frances H. Arnold

We engineered light-gated channelrhodopsins (ChRs) whose current strength and light sensitivity enable minimally invasive neuronal circuit interrogation. Current ChR tools applied to the mammalian brain require intracranial surgery for transgene delivery and implantation of fiber-optic cables to produce light-dependent activation of a small volume of tissue. To facilitate expansive optogenetics without the need for invasive implants, our engineering approach leverages the substantial literature of ChR variants to train statistical models for the design of high-performance ChRs. With Gaussian process models trained on a limited experimental set of 102 functionally characterized ChRs, we designed high-photocurrent ChRs with high light sensitivity. Three of these, ChRger1–3, enable optogenetic activation of the nervous system via systemic transgene delivery. ChRger2 enables light-induced neuronal excitation without fiber-optic implantation; that is, this opsin enables transcranial optogenetics. less

关键词： Machine Learning Optogenetics Statistical Calculation Neuronal Culture Electrophysiology Surgery Cell And Tissue Culture Microscopy Transfection Real-time PCR MATLAB Sequence Comparison Data analysis Python programming language GraphPad Prism GenBank Mus musculus Neuroscience Protein function predictions

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Statistical Methods for Identifying Biomarkers from miRNA Profiles of Cancers

Statistical Methods for Identifying Biomarkers from miRNA Pr...

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作者： Junghyun Namkung

Biomarkers play important roles in early diagnosis and treatment plan for cancer patients and the importance is growing. With advances in high-throughput molecular profiling technology for various types of molecules such as DNA, RNA, proteins, or metabolites, it is now possible to perform massive profiling analysis that allows accelerating discovery of novel biomolecules. Because no single marker is sufficiently accurate for clinical use, the cancer biomarker is developed in the form of multiple biomarker panels. No single marker is sufficiently accurate for clinical use, and thus cancer biomarkers are developed in the form of multiple biomarker panels. Of various types of molecular biomarkers, microRNA (miRNA) has emerged as a class of promising cancer biomarker recently. MiRNAs are small noncoding RNAs that regulate gene expression. The chapter overviews the process of identification of biomarker panels from miRNA profiles focusing on statistical methods. Introduction to molecular cancer biomarkers is touched first. From sample design to miRNA profiling process is reviewed in the method section. Statistical methods for biomarker development are introduced according to three typical purposes of molecular biomarkers: tumor subtype classification, early detection, and prediction of treatment response or prognosis of patients. Example codes for R program are provided as well for selected methods. less

关键词： Gene Expression Profiling Neural Network Model Decision Tree Regression Analysis Quantitative Reverse Transcription PCR Microarray Statistical Calculation RNA-seq Diagnostic Techniques Fractionation PCR Data analysis MicroRNA Sequencing programming language Biomarker identification Penalized regression Molecular subtype Cancer biomarker Cox proportional hazard model MiRNA profile

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Engineering of human cardiac muscle electromechanically matured to an adult-like phenotype

Engineering of human cardiac muscle electromechanically matu...

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作者： Kacey Ronaldson-Bouchard Keith Yeager Diogo Teles Timothy Chen Stephen Ma LouJin Song Kumi Morikawa Holly M. Wobma Alessandro Vasciaveo Edward C. Ruiz Masayuki Yazawa Gordana Vunjak-Novakovic

The application of tissue-engineering approaches to human induced pluripotent stem (hiPS) cells enables the development of physiologically relevant human tissue models for in vitro studies of development, regeneration, and disease. However, the immature phenotype of hiPS-derived cardiomyocytes (hiPS-CMs) limits their utility. We have developed a protocol to generate engineered cardiac tissues from hiPS cells and electromechanically mature them toward an adult-like phenotype. This protocol also provides optimized methods for analyzing these tissues’ functionality, ultrastructure, and cellular properties. The approach relies on biological adaptation of cultured tissues subjected to biomimetic cues, applied at an increasing intensity, to drive accelerated maturation. hiPS cells are differentiated into cardiomyocytes and used immediately after the first contractions are observed, when they still have developmental plasticity. This starting cell population is combined with human dermal fibroblasts, encapsulated in a fibrin hydrogel and allowed to compact under passive tension in a custom-designed bioreactor. After 7 d of tissue formation, the engineered tissues are matured for an additional 21 d by increasingly intense electromechanical stimulation. Tissue properties can be evaluated by measuring contractile function, responsiveness to electrical stimuli, ultrastructure properties (sarcomere length, mitochondrial density, networks of transverse tubules), force–frequency and force–length relationships, calcium handling, and responses to β-adrenergic agonists. Cell properties can be evaluated by monitoring gene/protein expression, oxidative metabolism, and electrophysiology. The protocol takes 4 weeks and requires experience in advanced cell culture and machining methods for bioreactor fabrication. We anticipate that this protocol will improve modeling of cardiac diseases and testing of drugs. less

关键词： Biomedical Engineering Cell And Tissue Culture Electrophysiology Tissue Engineering Immunostaining Flow Cytometry TEM Gene Expression Analysis Principal Component Analysis Long-term Culture Cross-linking MATLAB Confocal Microscopy High-throughput Screening Injection Molding Degassing ImageJ Calcium Imaging Paraffin Embedding Single-cell Sequencing MetaMorph Microscopy Image Analysis programming language Homo sapiens Mycoplasma Bos taurus Hippocampus Triticum aestivum Stem-cell differentiation Cardiovascular models Anti-sarcomeric α-actinin Anti-cTnT Anti-OxPhos Anti-mouse Anti-rabbit Anti-vimentin (VIM) Anti-human

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Computational Tools for Quantifying Concordance in Single-Cell Fate

Computational Tools for Quantifying Concordance in Single-Ce...

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作者： J. A. Cornwell R. E. Nordon

Cells are dynamic biological systems that interact with each other and their surrounding environment. Understanding how cell extrinsic and intrinsic factors control cell fate is fundamental to many biological experiments. However, due to transcriptional heterogeneity or microenvironmental fluctuations, cell fates appear to be random. Individual cells within well-defined subpopulations vary with respect to their proliferative potential, survival, and lineage potency. Therefore, methods to quantify fate outcomes for heterogeneous populations that consider both the stochastic and deterministic features of single-cell dynamics are required to develop accurate models of cell growth and differentiation. To study random versus deterministic cell behavior, one requires a probabilistic modelling approach to estimate cumulative incidence functions relating the probability of a cell’s fate to its lifetime and to model the deterministic effect of cell environment and inheritance, i.e., nature versus nurture. We have applied competing risks statistics, a branch of survival statistics, to quantify cell fate concordance from cell lifetime data. Competing risks modelling of cell fate concordance provides an unbiased, robust statistical modelling approach to model cell growth and differentiation by estimating the effect of cell extrinsic and heritable factors on the cause-specific cumulative incidence function. less

关键词： Statistical Calculation Regression Analysis Cell Tracking programming language Clonal analysis Single-cell fate mapping Concordance Competing risks

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Context-redefined language synthesis for energy consumption prediction using data from mixed remote sensors types 3

Context-redefined language synthesis for energy consumption ...

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Conference on Remote Sensing Technologies and Applications in Urban Environments III

作者： Belyaev, A. O. Podsvirov, V. N. Podoprigora, V. B. Sinutin, S. A. Boldyreff, A. S. Southern Fed Univ Inst Radiotech Syst & Control Engelsa Str 1 Taganrog Russia JSC RPE IC Kvant Milchakova 7 Rostov Na Donu Russia

ISBN: (纸本)9781510621701

This paper deals with the design and application issues of context-redefined computer languages for new information technologies. The discussion touches upon these languages implementation problems for intelligent learning agents (ILA), applied for solving the behavior prediction tasks for resource consumption in communal services. The article deals with the second problem in particular. The approach consists in the application of context-redefined language and its support system for problem solution. We focus on principal unpredicted changing of source function algorithms. Built-in context-redefined computer language is an essential tool for this kind of algorithm support. The main part of the intelligent learning agent is performance element. The performance element operates according to the current algorithm, which is described by means of built-in context-redefined language. The main idea of built-in language synthesis is to use main parts of the algorithm for ILA components with proper modification by means another algorithms and context connection. Due to this connection, the original algorithm can be changed directly or indirectly in the process of ILA functioning. We have to extract changing parts of component algorithms and organize proper interaction between every part and the context, which can be changed directly or indirectly. Required adaptive algorithm variation takes place on the base of obtained knowledge. At the same time, the algorithm must be implemented quickly, and the language must be simple and clear. The algorithm efficiency is based on flexibility and modifiability of the language. General constructions of the built-in context-redefined language have been demonstrated with proper comments.

关键词： energy consumption forecasting programming language intelligent learning agent context-redefined language smart city

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Work-in-Progress: VerticalThings - A language-based microkernel for constrained IoT devices 18

Work-in-Progress: VerticalThings - A language-based microker...

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18th ACM SIGBED International Conference on Embedded Software (EMSOFT)

作者： Poroor, Jayaraj Amrita Vishwa Vidyapeetham Sch Engn Dept Comp Sci & Engn Amritapuri India

ISBN: (纸本)9781538655603

A programming language that provides the functions of a secure microkernel is proposed for embedded and IoT applications. Towards this purpose, a type system based on the capability model is proposed, in which resource classes are abstracted as capability classes. Our language enables static analysis of key properties including safety, security, power, and timing considerations.

关键词： embedded systems programming language internet of things capabilities security kernel security access control IoT types refinement types

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An Overview of miRNA and miRNA Target Analysis Tools

An Overview of miRNA and miRNA Target Analysis Tools

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作者： Anna Lukasik Piotr Zielenkiewicz

microRNA molecules have been shown to play various significant roles in many physiological and pathophysiological processes in living organisms. The tremendous interest in these molecules has led to the significant development and constant release of a number of computational tools useful for basic as well as advanced miRNA-related analyses. These approaches have various constantly evolving utilities, such as detection, target prediction, functional annotation, and many others. In this chapter, we provide an overview of several computational tools useful for broadly defined plant miRNA analysis. less

关键词： Sequencing Analysis Tools High-Throughput Sequencing Differential Expression Analysis Deep Sequencing Genome Assembly Sequence Comparison Illumina Sequencing Bowtie Functional Enrichment HuntMi RNA-seq Statistical Calculation Quantitative Reverse Transcription PCR Data analysis bedtools Python programming language Analysis Bioinformatics miRNA Tools Prediction Target gene

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isoTar: Consensus Target Prediction with Enrichment Analysis for MicroRNAs Harboring Editing Sites and Other Variations

isoTar: Consensus Target Prediction with Enrichment Analysis...

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作者： Rosario Distefano Giovanni Nigita Dario Veneziano Giulia Romano Carlo M. Croce Mario Acunzo

MicroRNAs (miRNAs) are small noncoding RNA molecules (sncRNAs) involved in gene expression regulation. Having been widely studied during last two decades, they have been associated with several diseases, including cancer. Recent improvements in high throughput sequencing technologies have revealed a more complex miRNAome, due to miRNA sequence modification phenomena, such as RNA editing and isomiRs. As a result, a new class of tools is necessary in order to appropriately investigate this emerging complexity. To address such need, we developed isoTar, a high-performance Web-based containerized application designed for miRNA consensus targeting prediction and functional enrichment analyses. In the present chapter, we provide an overview of isoTar (https://***/isotar/ ), as well as benchmarks and a guide to its usage. less

关键词： High-Throughput Sequencing Functional Enrichment Python programming language Homo sapiens Malus domestica ADAR A-to-I RNA editing IsomiRs Editome

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Computational Proteomics with Jupyter and Python

Computational Proteomics with Jupyter and Python

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作者： Lars Malmström

Proteomics based on mass spectrometry produces complex data in large quantities. The need for flexible computational pipelines, in the context of big data, in proteomics and other areas of science, has prompted the development of computational platforms and libraries that facilitate data analysis and data processing. In this respect, Python appears to be one of the winners among programming languages in terms of popularity and development. This chapter shows how to perform basic tasks using Python and dedicated libraries in a Jupyter framework: from basic search result summarizations to the creation of MS1 chromatograms. less

关键词： Proteomics Mass Spectrometry Machine Learning Python Data analysis programming language R Jupyter Reproducible research JupyterHub

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A Reactive language for Analyzing Cloud Logs 5

A Reactive Language for Analyzing Cloud Logs

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5th ACM SIGPLAN International Workshop on Reactive and Event-Based languages and Systems (REBLS)

作者： Baudart, Guillaume Mandel, Louis Tardieu, Olivier Vaziri, Mandana IBM Res Yorktown Hts NY 10598 USA

ISBN: (纸本)9781450360708

Log analysis is required in many domains, and especially in the emerging field of cloud computing. Cloud applications are often built by composing diverse services. When something goes wrong, finding the root cause of the problem can be difficult. Many services are only reachable through their Application programming Interfaces (APIs) with no possibility for live introspection. In this context, logs become an essential tool for monitoring and debugging. Cloud services typically generate very large quantities of log messages, with formats that may not be well specified and may vary over time. In this paper, we present CloudLens, a language for the analysis of semi-structured textual data as found in logs, and specify its formal semantics. CloudLens is a reactive language and views logs as streams of objects. Our objective is to facilitate exploring the contents of logs interactively and to write reusable analyses succinctly, using familiar constructs. We implemented an interpreter for the Apache Zeppelin notebook to provide an interactive IDE. Our prototype implementation is open source and we report on a detailed case study using logs from the Apache OpenWhisk project.

关键词： Log analysis programming language Reactive programming

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