ResearchPad - simulation-and-modeling https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Mesh smoothing algorithm based on exterior angles split]]> https://www.researchpad.co/article/elastic_article_13823 Since meshes of poor quality give rise to low accuracy in finite element analysis and kinds of inconveniences in many other applications, mesh smoothing is widely used as an essential technique for the improvement of mesh quality. With respect to this issue, the main contribution of this paper is that a novel mesh smoothing method based on an exterior-angle-split process is proposed. The proposed method contains three main stages: the first stage is independent element geometric transformation performed by exterior-angle-split operations, treating elements unconnected; the second stage is to offset scaling and displacement induced by element transformation; the third stage is to determine the final positions of nodes with a weighted strategy. Theoretical proof describes the regularity of this method and many numerical experiments illustrate its convergence. Not only is this method applicable for triangular mesh, but also can be naturally extended to arbitrary polygonal surface mesh. Quality improvements of demonstrations on triangular and quadrilateral meshes show the effectiveness of this method.

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<![CDATA[The two types of society: Computationally revealing recurrent social formations and their evolutionary trajectories]]> https://www.researchpad.co/article/elastic_article_13873 Comparative social science has a long history of attempts to classify societies and cultures in terms of shared characteristics. However, only recently has it become feasible to conduct quantitative analysis of large historical datasets to mathematically approach the study of social complexity and classify shared societal characteristics. Such methods have the potential to identify recurrent social formations in human societies and contribute to social evolutionary theory. However, in order to achieve this potential, repeated studies are needed to assess the robustness of results to changing methods and data sets. Using an improved derivative of the Seshat: Global History Databank, we perform a clustering analysis of 271 past societies from sampling points across the globe to study plausible categorizations inherent in the data. Analysis indicates that the best fit to Seshat data is five subclusters existing as part of two clearly delineated superclusters (that is, two broad “types” of society in terms of social-ecological configuration). Our results add weight to the idea that human societies form recurrent social formations by replicating previous studies with different methods and data. Our results also contribute nuance to previously established measures of social complexity, illustrate diverse trajectories of change, and shed further light on the finite bounds of human social diversity.

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<![CDATA[Scedar: A scalable Python package for single-cell RNA-seq exploratory data analysis]]> https://www.researchpad.co/article/elastic_article_13837 In single-cell RNA-seq (scRNA-seq) experiments, the number of individual cells has increased exponentially, and the sequencing depth of each cell has decreased significantly. As a result, analyzing scRNA-seq data requires extensive considerations of program efficiency and method selection. In order to reduce the complexity of scRNA-seq data analysis, we present scedar, a scalable Python package for scRNA-seq exploratory data analysis. The package provides a convenient and reliable interface for performing visualization, imputation of gene dropouts, detection of rare transcriptomic profiles, and clustering on large-scale scRNA-seq datasets. The analytical methods are efficient, and they also do not assume that the data follow certain statistical distributions. The package is extensible and modular, which would facilitate the further development of functionalities for future requirements with the open-source development community. The scedar package is distributed under the terms of the MIT license at https://pypi.org/project/scedar.

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<![CDATA[A model for the assessment of bluetongue virus serotype 1 persistence in Spain]]> https://www.researchpad.co/article/elastic_article_11225 Bluetongue virus (BTV) is an arbovirus of ruminants that has been circulating in Europe continuously for more than two decades and has become endemic in some countries such as Spain. Spain is ideal for BTV epidemiological studies since BTV outbreaks from different sources and serotypes have occurred continuously there since 2000; BTV-1 has been reported there from 2007 to 2017. Here we develop a model for BTV-1 endemic scenario to estimate the risk of an area becoming endemic, as well as to identify the most influential factors for BTV-1 persistence. We created abundance maps at 1-km2 spatial resolution for the main vectors in Spain, Culicoides imicola and Obsoletus and Pulicaris complexes, by combining environmental satellite data with occurrence models and a random forest machine learning algorithm. The endemic model included vector abundance and host-related variables (farm density). The three most relevant variables in the endemic model were the abundance of C. imicola and Obsoletus complex and density of goat farms (AUC 0.86); this model suggests that BTV-1 is more likely to become endemic in central and southwestern regions of Spain. It only requires host- and vector-related variables to identify areas at greater risk of becoming endemic for bluetongue. Our results highlight the importance of suitable Culicoides spp. prediction maps for bluetongue epidemiological studies and decision-making about control and eradication measures.

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<![CDATA[Proficiency based progression simulation training significantly reduces utility strikes; A prospective, randomized and blinded study]]> https://www.researchpad.co/article/elastic_article_7871 We evaluated a simulation-based training curriculum with quantitatively defined performance benchmarks for utility workers location and excavation of utility services.BackgroundDamaging buried utilities is associated with considerable safety risks to workers and substantial cost to employers.MethodsIn a prospective, randomized and blinded study we assessed the impact of Proficiency Based Progression (PBP) simulation training on the location and excavation of utility services work.ResultsPBP simulation training reduced performance errors (33%, p = 0.006) in comparison a standard trained group. When implemented across all workers in the same division there was a 35–61% reduction in utility strikes (p = 0.028) and an estimated cost saving of £116,000 –£2,175,000 in the 12 months (47,000 work hours) studied.ConclusionsThe magnitude of the training benefit of PBP simulation training in the utilities sector appears to be the same as it is in surgery, cardiology and procedure-based medicine.ApplicationQuality-assured utility worker simulation training significantly reduces utility damage and associated costs. ]]> <![CDATA[Modeling competitive evolution of multiple languages]]> https://www.researchpad.co/article/elastic_article_7854 Increasing evidence demonstrates that in many places language coexistence has become ubiquitous and essential for supporting language and cultural diversity and associated with its financial and economic benefits. The competitive evolution among multiple languages determines the evolution outcome, either coexistence, or decline, or extinction. Here, we extend the Abrams-Strogatz model of language competition to multiple languages and then validate it by analyzing the behavioral transitions of language usage over the recent several decades in Singapore and Hong Kong. In each case, we estimate from data the model parameters that measure each language utility for its speakers and the strength of two biases, the majority preference for their language, and the minority aversion to it. The values of these two biases decide which language is the fastest growing in the competition and what would be the stable state of the system. We also study the system convergence time to stable states and discover the existence of tipping points with multiple attractors. Moreover, the critical slowdown of convergence to the stable fractions of language users appears near and peaks at the tipping points, signaling when the system approaches them. Our analysis furthers our understanding of evolution of various languages and the role of tipping points in behavioral transitions. These insights may help to protect languages from extinction and retain the language and cultural diversity.

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<![CDATA[Medusa: Software to build and analyze ensembles of genome-scale metabolic network reconstructions]]> https://www.researchpad.co/article/elastic_article_7734 Uncertainty in the structure and parameters of networks is ubiquitous across computational biology. In constraint-based reconstruction and analysis of metabolic networks, this uncertainty is present both during the reconstruction of networks and in simulations performed with them. Here, we present Medusa, a Python package for the generation and analysis of ensembles of genome-scale metabolic network reconstructions. Medusa builds on the COBRApy package for constraint-based reconstruction and analysis by compressing a set of models into a compact ensemble object, providing functions for the generation of ensembles using experimental data, and extending constraint-based analyses to ensemble scale. We demonstrate how Medusa can be used to generate ensembles and perform ensemble simulations, and how machine learning can be used in conjunction with Medusa to guide the curation of genome-scale metabolic network reconstructions. Medusa is available under the permissive MIT license from the Python Packaging Index (https://pypi.org) and from github (https://github.com/opencobra/Medusa), and comprehensive documentation is available at https://medusa.readthedocs.io/en/latest.

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<![CDATA[SimSurvey: An R package for comparing the design and analysis of surveys by simulating spatially-correlated populations]]> https://www.researchpad.co/article/elastic_article_8465 Populations often show complex spatial and temporal dynamics, creating challenges in designing and implementing effective surveys. Inappropriate sampling designs can potentially lead to both under-sampling (reducing precision) and over-sampling (through the extensive and potentially expensive sampling of correlated metrics). These issues can be difficult to identify and avoid in sample surveys of fish populations as they tend to be costly and comprised of multiple levels of sampling. Population estimates are therefore affected by each level of sampling as well as the pathway taken to analyze such data. Though simulations are a useful tool for exploring the efficacy of specific sampling strategies and statistical methods, there are a limited number of tools that facilitate the simulation testing of a range of sampling and analytical pathways for multi-stage survey data. Here we introduce the R package SimSurvey, which has been designed to simplify the process of simulating surveys of age-structured and spatially-distributed populations. The package allows the user to simulate age-structured populations that vary in space and time and explore the efficacy of a range of built-in or user-defined sampling protocols to reproduce the population parameters of the known population. SimSurvey also includes a function for estimating the stratified mean and variance of the population from the simulated survey data. We demonstrate the use of this package using a case study and show that it can reveal unexpected sources of bias and be used to explore design-based solutions to such problems. In summary, SimSurvey can serve as a convenient, accessible and flexible platform for simulating a wide range of sampling strategies for fish stocks and other populations that show complex structuring. Various statistical approaches can then be applied to the results to test the efficacy of different analytical approaches.

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<![CDATA[Genetic algorithm-based personalized models of human cardiac action potential]]> https://www.researchpad.co/article/elastic_article_7669 We present a novel modification of genetic algorithm (GA) which determines personalized parameters of cardiomyocyte electrophysiology model based on set of experimental human action potential (AP) recorded at different heart rates. In order to find the steady state solution, the optimized algorithm performs simultaneous search in the parametric and slow variables spaces. We demonstrate that several GA modifications are required for effective convergence. Firstly, we used Cauchy mutation along a random direction in the parametric space. Secondly, relatively large number of elite organisms (6–10% of the population passed on to new generation) was required for effective convergence. Test runs with synthetic AP as input data indicate that algorithm error is low for high amplitude ionic currents (1.6±1.6% for IKr, 3.2±3.5% for IK1, 3.9±3.5% for INa, 8.2±6.3% for ICaL). Experimental signal-to-noise ratio above 28 dB was required for high quality GA performance. GA was validated against optical mapping recordings of human ventricular AP and mRNA expression profile of donor hearts. In particular, GA output parameters were rescaled proportionally to mRNA levels ratio between patients. We have demonstrated that mRNA-based models predict the AP waveform dependence on heart rate with high precision. The latter also provides a novel technique of model personalization that makes it possible to map gene expression profile to cardiac function.

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<![CDATA[An electrodiffusive, ion conserving Pinsky-Rinzel model with homeostatic mechanisms]]> https://www.researchpad.co/article/elastic_article_7780 Neurons generate their electrical signals by letting ions pass through their membranes. Despite this fact, most models of neurons apply the simplifying assumption that ion concentrations remain effectively constant during neural activity. This assumption is often quite good, as neurons contain a set of homeostatic mechanisms that make sure that ion concentrations vary quite little under normal circumstances. However, under some conditions, these mechanisms can fail, and ion concentrations can vary quite dramatically. Standard models are thus not able to simulate such conditions. Here, we present what to our knowledge is the first multicompartmental neuron model that accounts for ion concentration variations in a way that ensures complete and consistent ion concentration and charge conservation. In this work, we use the model to explore under which activity conditions the ion concentration variations become important for predicting the neurodynamics. We expect the model to be of great value for the field of neuroscience, as it can be used to simulate a range of pathological conditions, such as spreading depression or epilepsy, which are associated with large changes in extracellular ion concentrations.

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<![CDATA[Time-lapse imaging of HeLa spheroids in soft agar culture provides virtual inner proliferative activity]]> https://www.researchpad.co/article/Nceafa1bd-f75c-4e08-9c15-587118f668b1

Cancer is a complex disease caused by multiple types of interactions. To simplify and normalize the assessment of drug effects, spheroid microenvironments have been utilized. Research models that involve agent measurement with the examination of clonogenic survival by monitoring culture process with image analysis have been developed for spheroid-based screening. Meanwhile, computer simulations using various models have enabled better predictions for phenomena in cancer. However, user-based parameters that are specific to a researcher’s own experimental conditions must be inputted. In order to bridge the gap between experimental and simulated conditions, we have developed an in silico analysis method with virtual three-dimensional embodiment computed using the researcher’s own samples. The present work focused on HeLa spheroid growth in soft agar culture, with spheroids being modeled in silico based on time-lapse images capturing spheroid growth. The spheroids in silico were optimized by adjusting the growth curves to those obtained from time-lapse images of spheroids and were then assigned virtual inner proliferative activity by using generations assigned to each cellular particle. The ratio and distribution of the virtual inner proliferative activities were confirmed to be similar to the proliferation zone ratio and histochemical profiles of HeLa spheroids, which were also consistent with those identified in an earlier study. We validated that time-lapse images of HeLa spheroids provided virtual inner proliferative activity for spheroids in vitro. The present work has achieved the first step toward an in silico analysis method using computational simulation based on a researcher’s own samples, helping to bridge the gap between experiment and simulation.

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<![CDATA[Class enumeration false positive in skew-t family of continuous growth mixture models]]> https://www.researchpad.co/article/Ne0623f60-4058-4fc0-9606-ac0f597752dc

Growth Mixture Modeling (GMM) has gained great popularity in the last decades as a methodology for longitudinal data analysis. The usual assumption of normally distributed repeated measures has been shown as problematic in real-life data applications. Namely, performing normal GMM on data that is even slightly skewed can lead to an over selection of the number of latent classes. In order to ameliorate this unwanted result, GMM based on the skew t family of continuous distributions has been proposed. This family of distributions includes the normal, skew normal, t, and skew t. This simulation study aims to determine the efficiency of selecting the “true” number of latent groups in GMM based on the skew t family of continuous distributions, using fit indices and likelihood ratio tests. Results show that the skew t GMM was the only model considered that showed fit indices and LRT false positive rates under the 0.05 cutoff value across sample sizes and for normal, and skewed and kurtic data. Simulation results are corroborated by a real educational data application example. These findings favor the development of practical guides of the benefits and risks of using the GMM based on this family of distributions.

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<![CDATA[Predicting 30-day hospital readmissions using artificial neural networks with medical code embedding]]> https://www.researchpad.co/article/N1f40719a-4631-45e6-bedb-5cf8a42ecf53

Reducing unplanned readmissions is a major focus of current hospital quality efforts. In order to avoid unfair penalization, administrators and policymakers use prediction models to adjust for the performance of hospitals from healthcare claims data. Regression-based models are a commonly utilized method for such risk-standardization across hospitals; however, these models often suffer in accuracy. In this study we, compare four prediction models for unplanned patient readmission for patients hospitalized with acute myocardial infarction (AMI), congestive health failure (HF), and pneumonia (PNA) within the Nationwide Readmissions Database in 2014. We evaluated hierarchical logistic regression and compared its performance with gradient boosting and two models that utilize artificial neural networks. We show that unsupervised Global Vector for Word Representations embedding representations of administrative claims data combined with artificial neural network classification models improves prediction of 30-day readmission. Our best models increased the AUC for prediction of 30-day readmissions from 0.68 to 0.72 for AMI, 0.60 to 0.64 for HF, and 0.63 to 0.68 for PNA compared to hierarchical logistic regression. Furthermore, risk-standardized hospital readmission rates calculated from our artificial neural network model that employed embeddings led to reclassification of approximately 10% of hospitals across categories of hospital performance. This finding suggests that prediction models that incorporate new methods classify hospitals differently than traditional regression-based approaches and that their role in assessing hospital performance warrants further investigation.

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<![CDATA[LoAdaBoost: Loss-based AdaBoost federated machine learning with reduced computational complexity on IID and non-IID intensive care data]]> https://www.researchpad.co/article/Na533cb35-b26a-447b-bd62-8e125a165db4

Intensive care data are valuable for improvement of health care, policy making and many other purposes. Vast amount of such data are stored in different locations, on many different devices and in different data silos. Sharing data among different sources is a big challenge due to regulatory, operational and security reasons. One potential solution is federated machine learning, which is a method that sends machine learning algorithms simultaneously to all data sources, trains models in each source and aggregates the learned models. This strategy allows utilization of valuable data without moving them. One challenge in applying federated machine learning is the possibly different distributions of data from diverse sources. To tackle this problem, we proposed an adaptive boosting method named LoAdaBoost that increases the efficiency of federated machine learning. Using intensive care unit data from hospitals, we investigated the performance of learning in IID and non-IID data distribution scenarios, and showed that the proposed LoAdaBoost method achieved higher predictive accuracy with lower computational complexity than the baseline method.

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<![CDATA[Exact flow of particles using for state estimations in unmanned aerial systems` navigation]]> https://www.researchpad.co/article/Nb8d1b185-24ca-4749-9cc9-bbc7ade34d0a

The navigation is a substantial issue in the field of robotics. Simultaneous Localization and Mapping (SLAM) is a principle for many autonomous navigation applications, particularly in the Global Navigation Satellite System (GNSS) denied environments. Many SLAM methods made substantial contributions to improve its accuracy, cost, and efficiency. Still, it is a considerable challenge to manage robust SLAM, and there exist several attempts to find better estimation algorithms for it. In this research, we proposed a novel Bayesian filtering based Airborne SLAM structure for the first time in the literature. We also presented the mathematical background of the algorithm, and the SLAM model of an autonomous aerial vehicle. Simulation results emphasize that the new Airborne SLAM performance with the exact flow of particles using for recursive state estimations superior to other approaches emerged before, in terms of accuracy and speed of convergence. Nevertheless, its computational complexity may cause real-time application concerns, particularly in high-dimensional state spaces. However, in Airborne SLAM, it can be preferred in the measurement environments that use low uncertainty sensors because it gives more successful results by eliminating the problem of degeneration seen in the particle filter structure.

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<![CDATA[Effect of internal surface structure of the north wall on Chinese solar greenhouse thermal microclimate based on computational fluid dynamics]]> https://www.researchpad.co/article/Nf5b70015-c0ce-4e08-9dc5-5525c2c91d69

Chinese solar greenhouses are unique facility agriculture buildings and widely used in northeastern China, providing a favorable requirement for crop growth. The north wall configurations play an essential role in heat storage and thermal insulation and directly affect the management of the internal environment. This research is devoted to further improve the thermal performance of the greenhouse and explore the potential of the north wall. A mathematical model was designed to investigate the concave-convex wall configurations based on computational fluid dynamics. Four passive heat-storage north walls were analyzed by using the same constituent materials, including a plane wall, a vertical wall, a horizontal wall and an alveolate wall. The numerical model was validated by experimental measurements. The temperature distributions of the north walls were examined and a comparative analysis of the heat storage-release capabilities was carried out. The results showed that the heat-storage capacity of the north wall is affected by the surface structure. Moreover, the critical factor influencing the air temperature is the sum of the heat load released by the wall and the energy increment of greenhouse air. The results suggested that the alveolate wall has preferable thermal accumulation capacity. The concave-convex wall configurations have a wider range of heat transfer performance along the thickness direction, while the plane wall has a superior thermal environment. This study provides a basic theoretical reference to rationally design the internal surface structures of the north wall.

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<![CDATA[Is it time to stop sweeping data cleaning under the carpet? A novel algorithm for outlier management in growth data]]> https://www.researchpad.co/article/N6ac4201b-e1d9-4dac-b706-1c6b88e127a6

All data are prone to error and require data cleaning prior to analysis. An important example is longitudinal growth data, for which there are no universally agreed standard methods for identifying and removing implausible values and many existing methods have limitations that restrict their usage across different domains. A decision-making algorithm that modified or deleted growth measurements based on a combination of pre-defined cut-offs and logic rules was designed. Five data cleaning methods for growth were tested with and without the addition of the algorithm and applied to five different longitudinal growth datasets: four uncleaned canine weight or height datasets and one pre-cleaned human weight dataset with randomly simulated errors. Prior to the addition of the algorithm, data cleaning based on non-linear mixed effects models was the most effective in all datasets and had on average a minimum of 26.00% higher sensitivity and 0.12% higher specificity than other methods. Data cleaning methods using the algorithm had improved data preservation and were capable of correcting simulated errors according to the gold standard; returning a value to its original state prior to error simulation. The algorithm improved the performance of all data cleaning methods and increased the average sensitivity and specificity of the non-linear mixed effects model method by 7.68% and 0.42% respectively. Using non-linear mixed effects models combined with the algorithm to clean data allows individual growth trajectories to vary from the population by using repeated longitudinal measurements, identifies consecutive errors or those within the first data entry, avoids the requirement for a minimum number of data entries, preserves data where possible by correcting errors rather than deleting them and removes duplications intelligently. This algorithm is broadly applicable to data cleaning anthropometric data in different mammalian species and could be adapted for use in a range of other domains.

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<![CDATA[Height of overburden fracture based on key strata theory in longwall face]]> https://www.researchpad.co/article/Nb6c965ed-0040-4b7a-b381-dffd2122531d

Among the three overburden zones (the caving zone, the fracture zone, and the continuous deformation zone) in longwall coal mining, the continuous deformation zone is often considered to be continuous without cracks, so continuum mechanics can be used to calculate the subsidence of overburden strata. Longwall coal mining, however, will induce the generation of wide cracks in the surface and thus may cause the continuous deformation zone to fracture. In this paper, whether there are cracks in the continuous deformation zone as well as the height of overburden fracture in longwall face and the subsidence and deformation of strata of different fracture penetration ratios were studied by means of physical simulation, theoretical analysis and numerical simulation. The results show that: (1) Rock stratum starts to fracture as long as it has slightly subsided for only tens of millimeters, and the height of fracture development is the height of working face overburden. (2) With the increase of fracture penetration ratio, the subsidence of key strata remains basically unchanged; the surface deformation range and the maximum compression deformation decrease, while the maximum horizontal movement and maximum horizontal tensile deformation increase. Therefore, the subsidence of overburden strata which have fractured but have not broken can be calculated through the continuum mechanics method.

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<![CDATA[Lean back and wait for the alarm? Testing an automated alarm system for nosocomial outbreaks to provide support for infection control professionals]]> https://www.researchpad.co/article/N4571fdc0-2a2e-4467-acc9-eeadc2652757

Introduction

Outbreaks of communicable diseases in hospitals need to be quickly detected in order to enable immediate control. The increasing digitalization of hospital data processing offers potential solutions for automated outbreak detection systems (AODS). Our goal was to assess a newly developed AODS.

Methods

Our AODS was based on the diagnostic results of routine clinical microbiological examinations. The system prospectively counted detections per bacterial pathogen over time for the years 2016 and 2017. The baseline data covers data from 2013–2015. The comparative analysis was based on six different mathematical algorithms (normal/Poisson and score prediction intervals, the early aberration reporting system, negative binomial CUSUMs, and the Farrington algorithm). The clusters automatically detected were then compared with the results of our manual outbreak detection system.

Results

During the analysis period, 14 different hospital outbreaks were detected as a result of conventional manual outbreak detection. Based on the pathogens’ overall incidence, outbreaks were divided into two categories: outbreaks with rarely detected pathogens (sporadic) and outbreaks with often detected pathogens (endemic). For outbreaks with sporadic pathogens, the detection rate of our AODS ranged from 83% to 100%. Every algorithm detected 6 of 7 outbreaks with a sporadic pathogen. The AODS identified outbreaks with an endemic pathogen were at a detection rate of 33% to 100%. For endemic pathogens, the results varied based on the epidemiological characteristics of each outbreak and pathogen.

Conclusion

AODS for hospitals based on routine microbiological data is feasible and can provide relevant benefits for infection control teams. It offers in-time automated notification of suspected pathogen clusters especially for sporadically occurring pathogens. However, outbreaks of endemically detected pathogens need further individual pathogen-specific and setting-specific adjustments.

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<![CDATA[A graph-based algorithm for RNA-seq data normalization]]> https://www.researchpad.co/article/N0b813aa9-b155-4778-93ba-b0f37d26ae8a

The use of RNA-sequencing has garnered much attention in recent years for characterizing and understanding various biological systems. However, it remains a major challenge to gain insights from a large number of RNA-seq experiments collectively, due to the normalization problem. Normalization has been challenging due to an inherent circularity, requiring that RNA-seq data be normalized before any pattern of differential (or non-differential) expression can be ascertained; meanwhile, the prior knowledge of non-differential transcripts is crucial to the normalization process. Some methods have successfully overcome this problem by the assumption that most transcripts are not differentially expressed. However, when RNA-seq profiles become more abundant and heterogeneous, this assumption fails to hold, leading to erroneous normalization. We present a normalization procedure that does not rely on this assumption, nor prior knowledge about the reference transcripts. This algorithm is based on a graph constructed from intrinsic correlations among RNA-seq transcripts and seeks to identify a set of densely connected vertices as references. Application of this algorithm on our synthesized validation data showed that it could recover the reference transcripts with high precision, thus resulting in high-quality normalization. On a realistic data set from the ENCODE project, this algorithm gave good results and could finish in a reasonable time. These preliminary results imply that we may be able to break the long persisting circularity problem in RNA-seq normalization.

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