scholarly journals An Automated Model Test System for Systematic Development and Improvement of Gene Expression Models

2020 ◽  
Vol 9 (11) ◽  
pp. 3145-3156
Author(s):  
Alexander C. Reis ◽  
Howard M. Salis
Keyword(s):  
Gene Expression ◽  
Model Test ◽  
Test System ◽  
Systematic Development

scholarly journals An automated model test system for systematic development and improvement of gene expression models

2017 ◽  
Author(s):  
Alexander C. Reis ◽  
Howard M. Salis
Keyword(s):  
Gene Expression ◽  
Model Test ◽  
Translation Initiation ◽  
Test System ◽  
Biophysical Model ◽  
Genetic Circuits ◽  
Initiation Rate ◽  
Information Theoretic ◽  
New Information ◽  
Genetic Systems

ABSTRACTGene expression models greatly accelerate the engineering of synthetic metabolic pathways and genetic circuits by predicting sequence-function relationships and reducing trial-and-error experimentation. However, developing models with more accurate predictions is a significant challenge, even though they are essential to engineering complex genetic systems. Here we present a model test system that combines advanced statistics, machine learning, and a database of 9862 characterized genetic systems to automatically quantify model accuracies, accept or reject mechanistic hypotheses, and identify areas for model improvement. We also introduce Model Capacity, a new information theoretic metric that enables correct model comparisons across datasets. We demonstrate the model test system by comparing six models of translation initiation rate, evaluating 100 mechanistic hypotheses, and uncovering new sequence determinants that control protein expression levels. We applied these results to develop a biophysical model of translation initiation rate with significant improvements in accuracy. Automated model test systems will dramatically accelerate the development of gene expression models, and thereby transition synthetic biology into a mature engineering discipline.

Development and preliminary application of a plate loading model test system considering stress state

Measurement ◽  
2021 ◽  
pp. 109507
Author(s):  
Changqi Zhu ◽  
Xing Wang ◽  
Mingjian Hu ◽  
Xinzhi Wang ◽  
Jianhua Shen ◽  
...  
Keyword(s):  
Stress State ◽  
Model Test ◽  
Test System ◽  
Preliminary Application ◽  
Plate Loading

Application and Development of Dynamic Loading Model Test System of Pile Based on FBG

IACGE 2018 ◽  
2019 ◽  
Author(s):  
Lei Gao ◽  
Han Long Liu ◽  
Xiangjuan Yu ◽  
Huidong Chen ◽  
Ali H. Mahfouz
Keyword(s):  
Dynamic Loading ◽  
Model Test ◽  
Test System

Development of compound EPB shield model test system for studying the water inrushes in karst regions

2020 ◽  
Vol 101 ◽  
pp. 103404 ◽  
Author(s):  
Liping Li ◽  
Shangqu Sun ◽  
Jing Wang ◽  
Shuguang Song ◽  
Zhongdong Fang ◽  
...  
Keyword(s):  
Model Test ◽  
Test System ◽  
Epb Shield

Development of DDPCR blood-based diagnostic tests that simultaneously measure mRNA expression from immune and cancer cells.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 22-22
Author(s):  
Hestia S. Mellert ◽  
Leisa Jackson ◽  
Chris Tompkins ◽  
Anne Lodge ◽  
Gary Anthony Pestano
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Evaluation Criteria ◽  
Prognostic Indicator ◽  
Digital Pcr ◽  
Test System ◽  
Wild Type ◽  
Assay Sensitivity ◽  
Healthy Donors ◽  
Circulating Rna

22 Background: Therapeutic options for patients with non-small cell lung cancer (NSCLC) continue to expand with the advent of immunotherapies. Lack of tissue and drawbacks with available IHC tests have increased the need for blood-based diagnostics. Thus, the detection of circulating nucleic acids has become highly relevant to clinical testing. Methods: We focused on extending the utility of blood-based testing for measurement of intra-cellular transcripts to multiplexed detection of gene expression. Specifically, we addressed maximizing the yield of quality circulating RNA for use in multiplexed droplet digital PCR (ddPCR) assays. Evaluation criteria included droplet counts for biomarkers of cancer and immunotherapy response. The markers evaluated were CD45, CD3, CK8, CK18, CK19, and PD-L1. Specimens included cell lines and prospectively collected samples from normal, healthy donors and donors with NSCLC. Results: Cell lines expressing variable levels of cytokeratins and PD-L1 were used to establish assay sensitivity. In these experiments, the test system could detect these markers in the equivalent of a single cell. We evaluated specificity using RNA from these same cell lines, resting and activated lymphocytes, and monocytes. With the exception of CK8, all assays demonstrated the expected specificities. Given the complexity of assessing PD-L1 in circulation because of its expression on immune cells, a threshold of 30 copies of PD-L1 was established using normal healthy donors (n = 9). Using this cut-off we then measured PD-L1 in circulating RNA from donors with NSCLC (n = 20). By these criteria, PD-L1 expression of sufficient copy number was restricted to a single EGFR wild-type donor (1/10). Previous reports have indicated that for EGFR wild-type patients, PD-L1 over expression may be considered a poor prognostic indicator of OS. Conclusions: We are developing sensitive and specific methods that can be applied to gene expression studies in blood. We have shown feasibility of these methods by evaluating key immune and cancer-specific RNAs. Evaluations are on-going with prospective sample collections to validate thresholds for this assay that may lead to its clinical utility.

Genotoxicity test system based on p53R2 gene expression in human cells: Examination with 80 chemicals

2005 ◽  
Vol 588 (1) ◽  
pp. 47-57 ◽  
Author(s):  
Katsutoshi Ohno ◽  
Yukimasa Tanaka-Azuma ◽  
Yukio Yoneda ◽  
Toshihiro Yamada
Keyword(s):  
Gene Expression ◽  
Test System ◽  
Human Cells ◽  
Genotoxicity Test

Transcriptional profiling of tissue plasticity: role of shifts in gene expression and technical limitations

2005 ◽  
Vol 99 (2) ◽  
pp. 397-413 ◽  
Author(s):  
Martin Flück ◽  
Christoph Däpp ◽  
Silvia Schmutz ◽  
Ernst Wit ◽  
Hans Hoppeler
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Expression Profiling ◽  
Transcriptional Profiling ◽  
Test System ◽  
Muscle Plasticity ◽  
Nucleolar Activity ◽  
Biological Outcomes ◽  
Rna And Dna

Reprogramming of gene expression has been recognized as a main instructive modality for the adjustments of tissues to various kinds of stress. The recent application of gene expression profiling has provided a powerful tool to elucidate the molecular pathways underlying such tissue remodeling. However, the biological interpretations of expression profiling results critically depend on normalization of transcript signals to mRNA standards before statistical evaluation. A hypothesis is proposed whereby the “fluctuating nature” of gene expression represents an inherent limitation of the test system used to quantify RNA levels. Misinterpretation of gene expression data occurs when RNA quantities are normalized to a subset of mRNAs that are subject to strong regulation. The contention of contradictory biological outcomes using different RNA-normalization schemes is demonstrated in two models of skeletal muscle plasticity with data from custom-designed microarrays and biochemical and ultrastructural evidence for correspondingly altered RNA content and nucleolar activity. The prevalence of these biological constraints is underlined by a literature survey in different models of tissue plasticity with emphasis on the unique malleability of skeletal muscle. Finally, recommendations on the optimal experimental layout are given to control biological and technical variability in microarray and RT-PCR studies. It is proposed to approach normalization of transcript signals by measuring total RNA and DNA content per sample weight and by correcting for concurrently estimated endogenous standards such as major ribosomal RNAs and spiked RNA and DNA species. This allows for later conversion to diverse tissue-relevant references and should improve the physiological interpretations of phenotypic plasticity.

A Large-Scale Model Test System for Stability Study of Tunnel Under Static-Dynamic Load

2021 ◽  
Author(s):  
Shucai Li ◽  
Bing Zhang ◽  
Hanpeng Wang ◽  
Wei Wang ◽  
Fei Xu ◽  
...  
Keyword(s):  
Model Test ◽  
Dynamic Load ◽  
Large Scale ◽  
Test System ◽  
Stability Study ◽  
Scale Model ◽  
Large Scale Model
Sign in / Sign up

Export Citation Format

Share Document