An ensemble of classifiers based on different texture descriptors for texture classification

Abstract Here we propose a system that incorporates two different state-of-the-art classifiers (support vector machine and gaussian process classifier) and two different descriptors (multi local quinary patterns and multi local phase quantization with ternary coding) for texture classification. Both the tested descriptors are an ensemble of stand-alone descriptors obtained using different parameters setting (the same set is used in each dataset). For each stand-alone descriptor we train a different classifier, the set of scores of each classifier is normalized to mean equal to zero and standard deviation equal to one, then all the score sets are combined by the sum rule. Our experimental section shows that we succeed in building a high performance ensemble that works well on different datasets without any ad hoc parameters tuning. The fusion among the different systems permits to outperform SVM where the parameters and kernels are tuned separately in each dataset, while in the proposed ensemble the linear SVM, with the same parameter cost in all the datasets, is used

Modellistica computazionale di cardiomiociti derivati da cellule staminali umane - Texture descriptor per l'elaborazione di immagini biologiche

This thesis investigates two distinct research topics. The main topic (Part I) is the computational modelling of cardiomyocytes derived from human stem cells, both embryonic (hESC-CM) and induced-pluripotent (hiPSC-CM). The aim of this research line lies in developing models of the electrophysiology of hESC-CM and hiPSC-CM in order to integrate the available experimental data and getting in-silico models to be used for studying/making new hypotheses/planning experiments on aspects not fully understood yet, such as the maturation process, the functionality of the Ca2+ hangling or why the hESC-CM/hiPSC-CM action potentials (APs) show some differences with respect to APs from adult cardiomyocytes. Chapter I.1 introduces the main concepts about hESC-CMs/hiPSC-CMs, the cardiac AP, and computational modelling. Chapter I.2 presents the hESC-CM AP model, able to simulate the maturation process through two developmental stages, Early and Late, based on experimental and literature data. Chapter I.3 describes the hiPSC-CM AP model, able to simulate the ventricular-like and atrial-like phenotypes. This model was used to assess which currents are responsible for the differences between the ventricular-like AP and the adult ventricular AP. The secondary topic (Part II) consists in the study of texture descriptors for biological image processing. Chapter II.1 provides an overview on important texture descriptors such as Local Binary Pattern or Local Phase Quantization. Moreover the non-binary coding and the multi-threshold approach are here introduced. Chapter II.2 shows that the non-binary coding and the multi-threshold approach improve the classification performance of cellular/sub-cellular part images, taken from six datasets. Chapter II.3 describes the case study of the classification of indirect immunofluorescence images of HEp2 cells, used for the antinuclear antibody clinical test. Finally the general conclusions are reported.Questa tesi indaga due distinti temi di ricerca. Il tema principale (Parte I) è la modellistica computazionale di cardiomiociti derivati da cellule staminali umane, sia embrionali (hESC-CM) che pluripotenti-indotte (hiPSC-CM). Lo scopo di questa parte consiste nello sviluppare modelli elettrofisiologici di hESC-CM e hiPSC-CM al fine di integrare i dati sperimentali disponibili ed ottenere modelli in-silico utilizzabili per studiare/produrre ipotesi/pianificare esperimenti su aspetti ancora poco chiari come il processo di maturazione, la funzionalità del Ca2+ handling e le cause per cui i potenziali d'azione(PA)di hESC-CM/hiPSC-CM mostrino alcune differenze rispetto ai PA di cardiomiociti adulti. Il capitolo I.1 introduce i concetti base su hESC-CM/hiPSC-CM, PA cardiaco e modellistica computazionale. Il capitolo I.2 presenta il modello di PA di hESC-CM in grado di riprodurre il processo di maturazione attraverso due stadi di sviluppo, Early e Late, basato su esperimenti e dati di letteratura. Il capitolo I.3 descrive il modello di PA di hiPSC-CM, in grado di riprodurre i fenotipi ventricular-like ed atrial-like. Questo modello è stato utilizzato per valutare quali correnti siano le principali responsabili delle differenze tra il PA ventricular-like e quello di cardiomiociti ventricolari adulti. Il tema secondario (Parte II) consiste nello studio di texture descriptor per la classificazione di immagini biologiche. Nel capitolo II.1 viene fornita una panoramica dei principali texture descriptor come Local Binary Pattern e Local Phase Quantization. Inoltre viene presentato il concetto di codifica non-binaria e approccio multi-threshold. Il Capitolo II.2 mostra che l'utilizzo della codifica non-binaria e dell'approccio multi-threshold portano ad un incremento delle performance di classificazione su sei dataset di immagini cellulari o di parti subcellulari. Il capitolo II.3 presenta un caso di studio di classificazione di immagini di immunofluorescenza indiretta su cellule HEp2, utilizzate in clinica per il test degli anticorpi antinucleo. Infine vengono riportate le conclusioni generali

Deep learning for actinic keratosis classification

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Audiogmenter: a MATLAB Toolbox for Audio Data Augmentation

Audio data augmentation is a key step in training deep neural networks for solving audio classification tasks. In this paper, we introduce Audiogmenter, a novel audio data augmentation library in MATLAB. We provide 15 different augmentation algorithms for raw audio data and 8 for spectrograms. We efficiently implemented several augmentation techniques whose usefulness has been extensively proved in the literature. To the best of our knowledge, this is the largest MATLAB audio data augmentation library freely available. We validate the efficiency of our algorithms evaluating them on the ESC-50 dataset. The toolbox and its documentation can be downloaded at https://github.com/LorisNanni/Audiogmenter

Comparison of Different Convolutional Neural Network Activation Functions and Methods for Building Ensembles for Small to Midsize Medical Data Sets

CNNs and other deep learners are now state-of-the-art in medical imaging research. However, the small sample size of many medical data sets dampens performance and results in overfitting. In some medical areas, it is simply too labor-intensive and expensive to amass images numbering in the hundreds of thousands. Building Deep CNN ensembles of pre-trained CNNs is one powerful method for overcoming this problem. Ensembles combine the outputs of multiple classifiers to improve performance. This method relies on the introduction of diversity, which can be introduced on many levels in the classification workflow. A recent ensembling method that has shown promise is to vary the activation functions in a set of CNNs or within different layers of a single CNN. This study aims to examine the performance of both methods using a large set of twenty activations functions, six of which are presented here for the first time: 2D Mexican ReLU, TanELU, MeLU + GaLU, Symmetric MeLU, Symmetric GaLU, and Flexible MeLU. The proposed method was tested on fifteen medical data sets representing various classification tasks. The best performing ensemble combined two well-known CNNs (VGG16 and ResNet50) whose standard ReLU activation layers were randomly replaced with another. Results demonstrate the superiority in performance of this approach.publishedVersionPeer reviewe

From multiscale biophysics to digital twins of tissues and organs: future opportunities for in silico pharmacology

With many advancements in in silico biology in recent years, the paramount challenge is to translate the accumulated knowledge into exciting industry partnerships and clinical applications. Achieving models that characterize the link of molecular interactions to the activity and structure of a whole organ are termed multiscale biophysics. Historically, the pharmaceutical industry has worked well with in silico models by leveraging their prediction capabilities for drug testing. However, the needed higher fidelity and higher resolution of models for efficient prediction of pharmacological phenomenon dictates that in silico approaches must account for the verifiable multiscale biophysical phenomena, as a spatial and temporal dimension variation for different processes and models. The collection of different multiscale models for different tissues and organs can compose digital twin solutions towards becoming a service for researchers, clinicians, and drug developers. Our paper has two main goals: 1) To clarify to what extent detailed single- and multiscale modeling has been accomplished thus far, we provide a review on this topic focusing on the biophysics of epithelial, cardiac, and brain tissues; 2) To discuss the present and future role of multiscale biophysics in in silico pharmacology as a digital twin solution by defining a roadmap from simple biophysical models to powerful prediction tools. Digital twins have the potential to pave the way for extensive clinical and pharmaceutical usage of multiscale models and our paper shows the basic fundamentals and opportunities towards their accurate development enabling the quantum leaps of future precise and personalized medical software.Comment: 30 pages, 10 figures, 1 tabl

Altered contractility in mutation-specific hypertrophic cardiomyopathy : A mechano-energetic in silico study with pharmacological insights

Introduction: Mavacamten (MAVA), Blebbistatin (BLEB), and Omecamtiv mecarbil (OM) are promising drugs directly targeting sarcomere dynamics, with demonstrated efficacy against hypertrophic cardiomyopathy (HCM) in (pre)clinical trials. However, the molecular mechanism affecting cardiac contractility regulation, and the diseased cell mechano-energetics are not fully understood yet.Methods: We present a new metabolite-sensitive computational model of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) electromechanics to investigate the pathology of R403Q HCM mutation and the effect of MAVA, BLEB, and OM on the cell mechano-energetics.Results: We offer a mechano-energetic HCM calibration of the model, capturing the prolonged contractile relaxation due to R403Q mutation (∼33%), without assuming any further modifications such as an additional Ca2+ flux to the thin filaments. The HCM model variant correctly predicts the negligible alteration in ATPase activity in R403Q HCM condition compared to normal hiPSC-CMs. The simulated inotropic effects of MAVA, OM, and BLEB, along with the ATPase activities in the control and HCM model variant agree with in vitro results from different labs. The proposed model recapitulates the tension-Ca2+ relationship and action potential duration change due to 1 µM OM and 5 µM BLEB, consistently with in vitro data. Finally, our model replicates the experimental dose-dependent effect of OM and BLEB on the normalized isometric tension.Conclusion: This work is a step toward deep-phenotyping the mutation-specific HCM pathophysiology, manifesting as altered interfilament kinetics. Accordingly, the modeling efforts lend original insights into the MAVA, BLEB, and OM contributions to a new interfilament balance resulting in a cardioprotective effect.publishedVersionPeer reviewe

TinderMIX : Time-dose integrated modelling of toxicogenomics data

Background: Omics technologies have been widely applied in toxicology studies to investigate the effects of different substances on exposed biological systems. A classical toxicogenomic study consists in testing the effects of a compound at different dose levels and different time points. The main challenge consists in identifying the gene alteration patterns that are correlated to doses and time points. The majority of existing methods for toxicogenomics data analysis allow the study of the molecular alteration after the exposure (or treatment) at each time point individually. However, this kind of analysis cannot identify dynamic (time-dependent) events of dose responsiveness. Results: We propose TinderMIX, an approach that simultaneously models the effects of time and dose on the transcriptome to investigate the course of molecular alterations exerted in response to the exposure. Starting from gene log fold-change, TinderMIX fits different integrated time and dose models to each gene, selects the optimal one, and computes its time and dose effect map; then a user-selected threshold is applied to identify the responsive area on each map and verify whether the gene shows a dynamic (time-dependent) and dose-dependent response; eventually, responsive genes are labelled according to the integrated time and dose point of departure. Conclusions: To showcase the TinderMIX method, we analysed 2 drugs from the Open TG-GATEs dataset, namely, cyclosporin A and thioacetamide. We first identified the dynamic dose-dependent mechanism of action of each drug and compared them. Our analysis highlights that different time- and dose-integrated point of departure recapitulates the toxicity potential of the compounds as well as their dynamic dose-dependent mechanism of action.Peer reviewe

Varied Image Data Augmentation Methods for Building Ensemble

Convolutional Neural Networks (CNNs) are used in many domains but the requirement of large datasets for robust training sessions and no overfitting makes them hard to apply in medical fields and similar fields. However, when large quantities of samples cannot be easily collected, various methods can still be applied to stem the problem depending on the sample type. Data augmentation, rather than other methods, has recently been under the spotlight mostly because of the simplicity and effectiveness of some of the more adopted methods. The research question addressed in this work is whether data augmentation techniques can help in developing robust and efficient machine learning systems to be used in different domains for classification purposes. To do that, we introduce new image augmentation techniques that make use of different methods like Fourier Transform (FT), Discrete Cosine Transform (DCT), Radon Transform (RT), Hilbert Transform (HT), Singular Value Decomposition (SVD), Local Laplacian Filters (LLF) and Hampel filter (HF). We define different ensemble methods by combining various classical data augmentation methods with the newer ones presented here. We performed an extensive empirical evaluation on 15 different datasets to validate our proposal. The obtained results show that the newly proposed data augmentation methods can be very effective even when used alone. The ensembles trained with different augmentations methods can outperform some of the best approaches reported in the literature as well as compete with state-of-the-art custom methods. All resources are available at https://github.com/LorisNanni.publishedVersionPeer reviewe