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1.
Mol Genet Genomics ; 298(1): 161-181, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36357622

RESUMO

MicroRNAs (miRNAs) play important role in regulating cellular metabolism, and are currently being explored in cancer. As metabolic reprogramming in cancer is a major mediator of phenotypic plasticity, understanding miRNA-regulated metabolism will provide opportunities to identify miRNA targets that can regulate oncogenic phenotypes by taking control of cellular metabolism. In the present work, we studied the effect of differentially expressed miRNAs on metabolism, and associated oncogenic phenotypes in glioblastoma (GBM) using patient-derived data. Networks of differentially expressed miRNAs and metabolic genes were created and analyzed to identify important miRNAs that regulate major metabolism in GBM. Graph network-based approaches like network diffusion, backbone extraction, and different centrality measures were used to analyze these networks for identification of potential miRNA targets. Important metabolic processes and cellular phenotypes were annotated to trace the functional responses associated with these miRNA-regulated metabolic genes and associated phenotype networks. miRNA-regulated metabolic gene subnetworks of cellular phenotypes were extracted, and important miRNAs regulating these phenotypes were identified. The most important outcome of the study is the target miRNA combinations predicted for five different oncogenic phenotypes that can be tested experimentally for miRNA-based therapeutic design in GBM. Strategies implemented in the study can be used to generate testable hypotheses in other cancer types as well, and design context-specific miRNA-based therapy for individual patient. Their usability can be further extended to other gene regulatory networks in cancer and other genetic diseases.


Assuntos
Glioblastoma , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Glioblastoma/genética , Glioblastoma/metabolismo , Perfilação da Expressão Gênica , Redes Reguladoras de Genes/genética , RNA Mensageiro/genética
2.
Appl Math Model ; 121: 506-523, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37234701

RESUMO

A new contagious disease or unidentified COVID-19 variants could provoke a new collapse in the global economy. Under such conditions, companies, factories, and organizations must adopt reopening policies that allow their operations to reduce economic effects. Effective reopening policies should be designed using mathematical models that emulate infection chains through individual interactions. In contrast to other modeling approaches, agent-based schemes represent a computational paradigm used to characterize the person-to-person interactions of individuals inside a system, providing accurate simulation results. To evaluate the optimal conditions for a reopening policy, authorities and decision-makers need to conduct an extensive number of simulations manually, with a high possibility of losing information and important details. For this reason, the integration of optimization and simulation of reopening policies could automatically find the realistic scenario under which the lowest risk of infection was attained. In this paper, the metaheuristic technique of the Whale Optimization Algorithm is used to find the solution with the minimal transmission risk produced by an agent-based model that emulates a hypothetical re-opening context. Our scheme finds the optimal results of different generical activation scenarios. The experimental results indicate that our approach delivers practical knowledge and essential estimations for identifying optimal re-opening strategies with the lowest transmission risk.

3.
Appl Soft Comput ; 128: 109464, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35966452

RESUMO

Pneumonia is one of the major reasons for child mortality especially in income-deprived regions of the world. Although it can be detected and treated with very less sophisticated instruments and medication, Pneumonia detection still remains a major concern in developing countries. Computer-aided based diagnosis (CAD) systems can be used in such countries due to their lower operating costs than professional medical experts. In this paper, we propose a CAD system for Pneumonia detection from Chest X-rays, using the concepts of deep learning and a meta-heuristic algorithm. We first extract deep features from the pre-trained ResNet50, fine-tuned on a target Pneumonia dataset. Then, we propose a feature selection technique based on particle swarm optimization (PSO), which is modified using a memory-based adaptation parameter, and enriched by incorporating an altruistic behavior into the agents. We name our feature selection method as adaptive and altruistic PSO (AAPSO). The proposed method successfully eliminates non-informative features obtained from the ResNet50 model, thereby improving the Pneumonia detection ability of the overall framework. Extensive experimentation and thorough analysis on a publicly available Pneumonia dataset establish the superiority of the proposed method over several other frameworks used for Pneumonia detection. Apart from Pneumonia detection, AAPSO is further evaluated on some standard UCI datasets, gene expression datasets for cancer prediction and a COVID-19 prediction dataset. The overall results are satisfactory, thereby confirming the usefulness of AAPSO in dealing with varied real-life problems. The supporting source codes of this work can be found at https://github.com/rishavpramanik/AAPSO.

4.
Expert Syst Appl ; 206: 117812, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35754941

RESUMO

The rapid outbreak of COVID-19 has affected the lives and livelihoods of a large part of the society. Hence, to confine the rapid spread of this virus, early detection of COVID-19 is extremely important. One of the most common ways of detecting COVID-19 is by using chest X-ray images. In the literature, it is found that most of the research activities applied convolutional neural network (CNN) models where the features generated by the last convolutional layer were directly passed to the classification models. In this paper, convolutional long short-term memory (ConvLSTM) layer is used in order to encode the spatial dependency among the feature maps obtained from the last convolutional layer of the CNN and to improve the image representational capability of the model. Additionally, the squeeze-and-excitation (SE) block, a spatial attention mechanism, is used to allocate weights to important local features. These two mechanisms are employed on three popular CNN models - VGG19, InceptionV3, and MobileNet to improve their classification strength. Finally, the Sugeno fuzzy integral based ensemble method is used on these classifiers' outputs to enhance the detection accuracy further. For experiments, three chest X-ray datasets, which are very prevalent for COVID-19 detection, are considered. For all the three datasets, it is found that the results obtained by the proposed method are comparable to state-of-the-art methods. The code, along with the pre-trained models, can be found at https://github.com/colabpro123/CovidConvLSTM.

5.
Expert Syst Appl ; 200: 116834, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36034050

RESUMO

Classification accuracy achieved by a machine learning technique depends on the feature set used in the learning process. However, it is often found that all the features extracted by some means for a particular task do not contribute to the classification process. Feature selection (FS) is an imperative and challenging pre-processing technique that helps to discard the unnecessary and irrelevant features while reducing the computational time and space requirement and increasing the classification accuracy. Generalized Normal Distribution Optimizer (GNDO), a recently proposed meta-heuristic algorithm, can be used to solve any optimization problem. In this paper, a hybrid version of GNDO with Simulated Annealing (SA) called Binary Simulated Normal Distribution Optimizer (BSNDO) is proposed which uses SA as a local search to achieve higher classification accuracy. The proposed method is evaluated on 18 well-known UCI datasets and compared with its predecessor as well as some popular FS methods. Moreover, this method is tested on high dimensional microarray datasets to prove its worth in real-life datasets. On top of that, it is also applied to a COVID-19 dataset for classification purposes. The obtained results prove the usefulness of BSNDO as a FS method. The source code of this work is publicly available at https://github.com/ahmed-shameem/Feature_selection.

6.
Expert Syst Appl ; 193: 116377, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35002099

RESUMO

Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It may cause serious ailments in infected individuals and complications may lead to death. X-rays and Computed Tomography (CT) scans can be used for the diagnosis of the disease. In this context, various methods have been proposed for the detection of COVID-19 from radiological images. In this work, we propose an end-to-end framework consisting of deep feature extraction followed by feature selection (FS) for the detection of COVID-19 from CT scan images. For feature extraction, we utilize three deep learning based Convolutional Neural Networks (CNNs). For FS, we use a meta-heuristic optimization algorithm, Harmony Search (HS), combined with a local search method, Adaptive ß -Hill Climbing (A ß HC) for better performance. We evaluate the proposed approach on the SARS-COV-2 CT-Scan Dataset consisting of 2482 CT scan images and an updated version of the previous dataset containing 2926 CT scan images. For comparison, we use a few state-of-the-art optimization algorithms. The best accuracy scores obtained by the present approach are 97.30% and 98.87% respectively on the said datasets, which are better than many of the algorithms used for comparison. The performances are also at par with some recent works which use the same datasets. The codes for the FS algorithms are available at: https://github.com/khalid0007/Metaheuristic-Algorithms.

7.
Measurement (Lond) ; 187: 110289, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34663998

RESUMO

Biomedical images contain a large volume of sensor measurements, which can reveal the descriptors of the disease under investigation. Computer-based analysis of such measurements helps detect the disease, and thereby swiftly aid medical professionals to choose adequate therapy. In this paper, we propose a robust deep learning ensemble framework known as COVID Fuzzy Ensemble Network, or COFE-Net. This strategy is proposed for the task of COVID-19 screening from chest X-rays (CXR) and CT Scans, as a part of Computer-Aided Detection (CADe) for medical practitioners. We leverage the strategy of Transfer Learning for Convolutional Neural Networks (CNNs) widely adopted in recent literature, and further propose an efficient ensemble network for their combination. The principles of fuzzy logic have been leveraged to combine the measured decision scores generated by three state-of-the-art CNNs - Inception V3, Inception ResNet V2 and DenseNet 201 - through the Choquet fuzzy integral. Experimental results support the efficacy of our approach over empirical ensembling, as the fuzzy ensembling strategy for biomedical measurement consists of dynamic refactoring of the classifier ensemble weights on the fly, based upon the confidence scores for coalitions of inputs. This is the chief advantage of our biomedical measurement strategy over others as other methods do not adjust to the multiple generated measurements dynamically unlike ours.Impressive results on multiple datasets demonstrate the effectiveness of the proposed method. The source code of our proposed method is made available at: https://github.com/theavicaster/covid-cade-ensemble.

8.
Sensors (Basel) ; 21(16)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34450866

RESUMO

Sleep Apnea is a breathing disorder occurring during sleep. Older people suffer most from this disease. In-time diagnosis of apnea is needed which can be observed by the application of a proper health monitoring system. In this work, we focus on Obstructive Sleep Apnea (OSA) detection from the Electrocardiogram (ECG) signals obtained through the body sensors. Our work mainly consists of an experimental study of different ensemble techniques applied on three deep learning models-two Convolutional Neural Network (CNN) based models, and a combination of CNN and Long Short-Term Memory (LSTM) models, which were previously proposed in the OSA detection domain. We have chosen four ensemble techniques-majority voting, sum rule and Choquet integral based fuzzy fusion and trainable ensemble using Multi-Layer Perceptron (MLP) for our case study. All the experiments are conducted on the benchmark PhysioNet Apnea-ECG Database. Finally, we have achieved highest OSA detection accuracy of 85.58% using the MLP based ensemble approach. Our best result is also able to surpass many of state-of-the-art methods.


Assuntos
Aprendizado Profundo , Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Idoso , Eletrocardiografia , Humanos , Redes Neurais de Computação , Polissonografia , Síndromes da Apneia do Sono/diagnóstico , Apneia Obstrutiva do Sono/diagnóstico
9.
Sensors (Basel) ; 21(16)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34451013

RESUMO

In machine learning and data science, feature selection is considered as a crucial step of data preprocessing. When we directly apply the raw data for classification or clustering purposes, sometimes we observe that the learning algorithms do not perform well. One possible reason for this is the presence of redundant, noisy, and non-informative features or attributes in the datasets. Hence, feature selection methods are used to identify the subset of relevant features that can maximize the model performance. Moreover, due to reduction in feature dimension, both training time and storage required by the model can be reduced as well. In this paper, we present a tri-stage wrapper-filter-based feature selection framework for the purpose of medical report-based disease detection. In the first stage, an ensemble was formed by four filter methods-Mutual Information, ReliefF, Chi Square, and Xvariance-and then each feature from the union set was assessed by three classification algorithms-support vector machine, naïve Bayes, and k-nearest neighbors-and an average accuracy was calculated. The features with higher accuracy were selected to obtain a preliminary subset of optimal features. In the second stage, Pearson correlation was used to discard highly correlated features. In these two stages, XGBoost classification algorithm was applied to obtain the most contributing features that, in turn, provide the best optimal subset. Then, in the final stage, we fed the obtained feature subset to a meta-heuristic algorithm, called whale optimization algorithm, in order to further reduce the feature set and to achieve higher accuracy. We evaluated the proposed feature selection framework on four publicly available disease datasets taken from the UCI machine learning repository, namely, arrhythmia, leukemia, DLBCL, and prostate cancer. Our obtained results confirm that the proposed method can perform better than many state-of-the-art methods and can detect important features as well. Less features ensure less medical tests for correct diagnosis, thus saving both time and cost.


Assuntos
Algoritmos , Máquina de Vetores de Suporte , Teorema de Bayes , Análise por Conglomerados , Humanos , Aprendizado de Máquina , Masculino
10.
Sensors (Basel) ; 21(11)2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-34071029

RESUMO

Breast cancer, like most forms of cancer, is a fatal disease that claims more than half a million lives every year. In 2020, breast cancer overtook lung cancer as the most commonly diagnosed form of cancer. Though extremely deadly, the survival rate and longevity increase substantially with early detection and diagnosis. The treatment protocol also varies with the stage of breast cancer. Diagnosis is typically done using histopathological slides from which it is possible to determine whether the tissue is in the Ductal Carcinoma In Situ (DCIS) stage, in which the cancerous cells have not spread into the encompassing breast tissue, or in the Invasive Ductal Carcinoma (IDC) stage, wherein the cells have penetrated into the neighboring tissues. IDC detection is extremely time-consuming and challenging for physicians. Hence, this can be modeled as an image classification task where pattern recognition and machine learning can be used to aid doctors and medical practitioners in making such crucial decisions. In the present paper, we use an IDC Breast Cancer dataset that contains 277,524 images (with 78,786 IDC positive images and 198,738 IDC negative images) to classify the images into IDC(+) and IDC(-). To that end, we use feature extractors, including textural features, such as SIFT, SURF and ORB, and statistical features, such as Haralick texture features. These features are then combined to yield a dataset of 782 features. These features are ensembled by stacking using various Machine Learning classifiers, such as Random Forest, Extra Trees, XGBoost, AdaBoost, CatBoost and Multi Layer Perceptron followed by feature selection using Pearson Correlation Coefficient to yield a dataset with four features that are then used for classification. From our experimental results, we found that CatBoost yielded the highest accuracy (92.55%), which is at par with other state-of-the-art results-most of which employ Deep Learning architectures. The source code is available in the GitHub repository.


Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Neoplasias da Mama/diagnóstico , Computadores , Humanos , Aprendizado de Máquina , Redes Neurais de Computação
11.
Sensors (Basel) ; 21(14)2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34300388

RESUMO

Handwritten keyword spotting (KWS) is of great interest to the document image research community. In this work, we propose a learning-free keyword spotting method following query by example (QBE) setting for handwritten documents. It consists of four key processes: pre-processing, vertical zone division, feature extraction, and feature matching. The pre-processing step deals with the noise found in the word images, and the skewness of the handwritings caused by the varied writing styles of the individuals. Next, the vertical zone division splits the word image into several zones. The number of vertical zones is guided by the number of letters in the query word image. To obtain this information (i.e., number of letters in a query word image) during experimentation, we use the text encoding of the query word image. The user provides the information to the system. The feature extraction process involves the use of the Hough transform. The last step is feature matching, which first compares the features extracted from the word images and then generates a similarity score. The performance of this algorithm has been tested on three publicly available datasets: IAM, QUWI, and ICDAR KWS 2015. It is noticed that the proposed method outperforms state-of-the-art learning-free KWS methods considered here for comparison while evaluated on the present datasets. We also evaluate the performance of the present KWS model using state-of-the-art deep features and it is found that the features used in the present work perform better than the deep features extracted using InceptionV3, VGG19, and DenseNet121 models.


Assuntos
Algoritmos , Armazenamento e Recuperação da Informação , Escrita Manual , Humanos
12.
Appl Soft Comput ; 111: 107698, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34276262

RESUMO

Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It may cause severe ailments in infected individuals. The more severe cases may lead to death. Automated methods which can detect COVID-19 in radiological images can help in the screening of patients. In this work, a two-stage pipeline composed of feature extraction followed by feature selection (FS) for the detection of COVID-19 from CT scan images is proposed. For feature extraction, a state-of-the-art Convolutional Neural Network (CNN) model based on the DenseNet architecture is utilised. To eliminate the non-informative and redundant features, the meta-heuristic called Harris Hawks optimisation (HHO) algorithm combined with Simulated Annealing (SA) and Chaotic initialisation is employed. The proposed approach is evaluated on the SARS-COV-2 CT-Scan dataset which consists of 2482 CT-scans. Without the Chaotic initialisation and the SA, the method gives an accuracy of around 98.42% which further increases to 98.85% on the inclusion of the two and thus delivers better performance than many state-of-the-art methods and various meta-heuristic based FS algorithms. Also, comparison has been drawn with many hybrid variants of meta-heuristic algorithms. Although HHO falls behind a few of the hybrid variants, when Chaotic initialisation and SA are incorporated into it, the proposed algorithm performs better than any other algorithm with which comparison has been drawn. The proposed algorithm decreases the number of features selected by around 75% , which is better than most of the other algorithms.

13.
Appl Intell (Dordr) ; 51(12): 8985-9000, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34764594

RESUMO

The rapid spread of coronavirus disease has become an example of the worst disruptive disasters of the century around the globe. To fight against the spread of this virus, clinical image analysis of chest CT (computed tomography) images can play an important role for an accurate diagnostic. In the present work, a bi-modular hybrid model is proposed to detect COVID-19 from the chest CT images. In the first module, we have used a Convolutional Neural Network (CNN) architecture to extract features from the chest CT images. In the second module, we have used a bi-stage feature selection (FS) approach to find out the most relevant features for the prediction of COVID and non-COVID cases from the chest CT images. At the first stage of FS, we have applied a guided FS methodology by employing two filter methods: Mutual Information (MI) and Relief-F, for the initial screening of the features obtained from the CNN model. In the second stage, Dragonfly algorithm (DA) has been used for the further selection of most relevant features. The final feature set has been used for the classification of the COVID-19 and non-COVID chest CT images using the Support Vector Machine (SVM) classifier. The proposed model has been tested on two open-access datasets: SARS-CoV-2 CT images and COVID-CT datasets and the model shows substantial prediction rates of 98.39% and 90.0% on the said datasets respectively. The proposed model has been compared with a few past works for the prediction of COVID-19 cases. The supporting codes are uploaded in the Github link: https://github.com/Soumyajit-Saha/A-Bi-Stage-Feature-Selection-on-Covid-19-Dataset.

14.
Proteins ; 88(3): 514-526, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31589795

RESUMO

Smoothened (SMO) antagonist Vismodegib effectively inhibits the Hedgehog pathway in proliferating cancer cells. In early stage of treatment, Vismodegib exhibited promising outcomes to regress the tumors cells, but ultimately relapsed due to the drug resistive mutations in SMO mostly occurring before (primary mutations G497W) or after (acquired mutations D473H/Y) anti-SMO therapy. This study investigates the unprecedented insights of structural and functional mechanism hindering the binding of Vismodegib with sensitive and resistant mutant variants of SMO (SMOMut ). Along with the basic dynamic understanding of Vismodegib-SMO complexes, network propagation theory based on heat diffusion principles is first time applied here to identify the modules of residues influenced by the individual mutations. The allosteric modulation by GLY497 residue in Vismodegib bound SMO wild-type (SMOWT ) conformation depicts the interconnections of intermediate residues of SMO with the atom of Vismodegib and identify two important motifs (E-X-P-L) and (Q-A-N-V-T-I-G) mediating this allosteric regulation. In this study a novel computational framework based on the heat diffusion principle is also developed, which identify significant residues of allosteric site causing drug resistivity in SMOMut . This framework could also be useful for assessing the potential allosteric sites of different other proteins. Moreover, previously reported novel inhibitor "ZINC12368305," which is proven to make an energetically favorable complex with SMOWT is chosen as a control sample to assess the impact of receptor mutation on its binding and subsequently identify the important factors that govern binding disparity between Vismodegib and ZINC12368305 bound SMOWT/Mut conformations.


Assuntos
Anilidas/química , Antineoplásicos/química , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas de Neoplasias/química , Piridinas/química , Receptor Smoothened/química , Regulação Alostérica , Sítio Alostérico , Anilidas/metabolismo , Anilidas/farmacologia , Antracenos/química , Antracenos/metabolismo , Antracenos/farmacologia , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Sítios de Ligação , Expressão Gênica , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Cinética , Simulação de Dinâmica Molecular , Mutação , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Fenantrenos/química , Fenantrenos/metabolismo , Fenantrenos/farmacologia , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Piridinas/metabolismo , Piridinas/farmacologia , Transdução de Sinais , Receptor Smoothened/antagonistas & inibidores , Receptor Smoothened/genética , Receptor Smoothened/metabolismo , Termodinâmica
15.
J Theor Biol ; 469: 61-74, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-30817925

RESUMO

Infectious disease and chemical contamination are increasingly becoming vital issues in many ecosystems. However, studies integrating the two are surprisingly rare. Contamination not only affects the inherent host-resource interaction which influences the epidemic process but may also directly affect epidemiological traits via changes in host's behaviour. The fact that heavy metal such as copper is also an essential trace element for organisms, further increase complexity which make predicting the resultant effect of contamination and disease spread difficult. Motivated by this, we model the effect of copper enrichment on a phytoplankton-zooplankton-fungus system. We show that extremely deficient or toxic copper may have a destabilizing effect on the underlying host-resource dynamics due to increased relative energy fluxes as a result of low host mortality due to fish predation. Further, on incorporating disease into the system, we find that the system can become disease-free for an intermediate range of copper concentration whereas it may persist for very less copper enrichment. Also, we predict that there may exist vulnerable regions of copper concentration near the toxic and deficient levels, where the parasite can invade the system for a comparatively lower spore yield. Overall, our results demonstrate that, the effect of contamination may be fundamental to understanding disease progression in community ecology.


Assuntos
Cobre/toxicidade , Epidemias , Poluentes Químicos da Água/toxicidade , Zooplâncton/efeitos dos fármacos , Animais , Simulação por Computador , Daphnia/efeitos dos fármacos , Interações Hospedeiro-Parasita/efeitos dos fármacos
16.
J Mol Evol ; 86(7): 443-456, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30022295

RESUMO

The sandfly midgut and the human macrophage phagolysosome provide antagonistic metabolic niches for the endoparasite Leishmania to survive and populate. Although these environments fluctuate across developmental stages, the relative changes in both these environments across parasite generations might remain gradual. Such environmental restrictions might endow parasite metabolism with a choice of specific genotypic and phenotypic factors that can constrain enzyme evolution for successful adaptation to the host. With respect to the available cellular information for Leishmania species, for the first time, we measure the relative contribution of eight inter-correlated predictors related to codon usage, GC content, gene expression, gene length, multi-functionality, and flux-coupling potential of an enzyme on the evolutionary rates of singleton metabolic genes and further compare their effects across three Leishmania species. Our analysis reveals that codon adaptation, multi-functionality, and flux-coupling potential of an enzyme are independent contributors of enzyme evolutionary rates, which can together explain a large variation in enzyme evolutionary rates across species. We also hypothesize that a species-specific occurrence of duplicated genes in novel subcellular locations can create new flux routes through certain singleton flux-coupled enzymes, thereby constraining their evolution. A cross-species comparison revealed both common and species-specific genes whose evolutionary divergence was constrained by multiple independent factors. Out of these, previously known pharmacological targets and virulence factors in Leishmania were identified, suggesting their evolutionary reasons for being important survival factors to the parasite. All these results provide a fundamental understanding of the factors underlying adaptive strategies of the parasite, which can be further targeted.


Assuntos
Leishmania/genética , Leishmania/metabolismo , Adaptação Fisiológica/genética , Composição de Bases/genética , Evolução Biológica , Códon/genética , Códon/metabolismo , Bases de Dados Genéticas , Evolução Molecular , Estudos de Associação Genética , Genômica/métodos , Genótipo , Especificidade da Espécie
17.
Phys Chem Chem Phys ; 20(35): 22987-22996, 2018 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-30156235

RESUMO

Classical force fields form a computationally efficient avenue for calculating the energetics of large systems. However, due to the constraints of the underlying analytical form, it is sometimes not accurate enough. Quantum mechanical (QM) methods, although accurate, are computationally prohibitive for large systems. In order to circumvent the bottle-neck of interaction energy estimation of large systems, data driven approaches based on machine learning (ML) have been employed in recent years. In most of these studies, the method of choice is artificial neural networks (ANN). In this work, we have shown an alternative ML method, support vector regression (SVR), that provides comparable accuracy with better computational efficiency. We have further used many body expansion (MBE) along with SVR to predict interaction energies in water clusters (decamers). In the case of dimer and trimer interaction energies, the root mean square errors (RMSEs) of the SVR based scheme are 0.12 kcal mol-1 and 0.34 kcal mol-1, respectively. We show that the SVR and MBE based scheme has a RMSE of 2.78% in the estimation of decamer interaction energy against the parent QM method in a computationally efficient way.

18.
Genomics ; 106(4): 232-41, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26043961

RESUMO

Understanding the variations in gene organization and its effect on the phenotype across different Leishmania species, and to study differential clinical manifestations of parasite within the host, we performed large scale analysis of codon usage patterns between Leishmania and other known Trypanosomatid species. We present the causes and consequences of codon usage bias in Leishmania genomes with respect to mutational pressure, translational selection and amino acid composition bias. We establish GC bias at wobble position that governs codon usage bias across Leishmania species, rather than amino acid composition bias. We found that, within Leishmania, homogenous codon context coding for less frequent amino acid pairs and codons avoiding formation of folding structures in mRNA are essentially chosen. We predicted putative differences in global expression between genes belonging to specific pathways across Leishmania. This explains the role of evolution in shaping the otherwise conserved genome to demonstrate species-specific function-level differences for efficient survival.


Assuntos
Leishmania/genética , Proteínas de Protozoários/análise , RNA Mensageiro/química , RNA de Protozoário/química , Trypanosomatina/genética , Sequência de Aminoácidos , Composição de Bases , Códon , Evolução Molecular , Leishmania/metabolismo , Mutação , Conformação de Ácido Nucleico , Especificidade da Espécie , Trypanosomatina/metabolismo
19.
R Soc Open Sci ; 11(3): 231574, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38481985

RESUMO

Tumour-immune microenvironment (TIME) is pivotal in tumour progression and immunoediting. Within TIME, immune cells undergo metabolic adjustments impacting nutrient supply and the anti-tumour immune response. Metabolic reprogramming emerges as a promising approach to revert the immune response towards a pro-inflammatory state and conquer tumour dominance. This study proposes immunomodulatory mechanisms based on metabolic reprogramming and employs the regulatory flux balance analysis modelling approach, which integrates signalling, metabolism and regulatory processes. For the first time, a comprehensive system-level model is constructed to capture signalling and metabolic cross-talks during tumour-immune interaction and regulatory constraints are incorporated by considering the time lag between them. The model analysis identifies novel features to enhance the immune response while suppressing tumour activity. Particularly, altering the exchange of succinate and oxaloacetate between glioma and macrophage enhances the pro-inflammatory response of immune cells. Inhibition of glutamate uptake in T-cells disrupts the antioxidant mechanism of glioma and reprograms metabolism. Metabolic reprogramming through adenosine monophosphate (AMP)-activated protein kinase (AMPK), coupled with glutamate uptake inhibition, was identified as the most impactful combination to restore T-cell function. A comprehensive understanding of metabolism and gene regulation represents a favourable approach to promote immune cell recovery from tumour dominance.

20.
PLoS One ; 19(5): e0303670, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38820462

RESUMO

Breast cancer remains a critical global concern, underscoring the urgent need for early detection and accurate diagnosis to improve survival rates among women. Recent developments in deep learning have shown promising potential for computer-aided detection (CAD) systems to address this challenge. In this study, a novel segmentation method based on deep learning is designed to detect tumors in breast ultrasound images. Our proposed approach combines two powerful attention mechanisms: the novel Positional Convolutional Block Attention Module (PCBAM) and Shifted Window Attention (SWA), integrated into a Residual U-Net model. The PCBAM enhances the Convolutional Block Attention Module (CBAM) by incorporating the Positional Attention Module (PAM), thereby improving the contextual information captured by CBAM and enhancing the model's ability to capture spatial relationships within local features. Additionally, we employ SWA within the bottleneck layer of the Residual U-Net to further enhance the model's performance. To evaluate our approach, we perform experiments using two widely used datasets of breast ultrasound images and the obtained results demonstrate its capability in accurately detecting tumors. Our approach achieves state-of-the-art performance with dice score of 74.23% and 78.58% on BUSI and UDIAT datasets, respectively in segmenting the breast tumor region, showcasing its potential to help with precise tumor detection. By leveraging the power of deep learning and integrating innovative attention mechanisms, our study contributes to the ongoing efforts to improve breast cancer detection and ultimately enhance women's survival rates. The source code of our work can be found here: https://github.com/AyushRoy2001/DAUNet.


Assuntos
Neoplasias da Mama , Aprendizado Profundo , Ultrassonografia Mamária , Humanos , Neoplasias da Mama/diagnóstico por imagem , Feminino , Ultrassonografia Mamária/métodos , Redes Neurais de Computação , Algoritmos , Interpretação de Imagem Assistida por Computador/métodos , Mama/diagnóstico por imagem , Mama/patologia , Processamento de Imagem Assistida por Computador/métodos
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