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1.
Brief Bioinform ; 23(5)2022 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-36088571

RESUMEN

Cell surface proteins have been used as diagnostic and prognostic markers in cancer research and as targets for the development of anticancer agents. Many of these proteins lie at the top of signaling cascades regulating cell responses and gene expression, therefore acting as 'signaling hubs'. It has been previously demonstrated that the integrated network analysis on transcriptomic data is able to infer cell surface protein activity in breast cancer. Such an approach has been implemented in a publicly available method called 'SURFACER'. SURFACER implements a network-based analysis of transcriptomic data focusing on the overall activity of curated surface proteins, with the final aim to identify those proteins driving major phenotypic changes at a network level, named surface signaling hubs. Here, we show the ability of SURFACER to discover relevant knowledge within and across cancer datasets. We also show how different cancers can be stratified in surface-activity-specific groups. Our strategy may identify cancer-wide markers to design targeted therapies and biomarker-based diagnostic approaches.


Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Proteínas de la Membrana/genética , Transcriptoma
2.
Bioinformatics ; 39(5)2023 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-37154702

RESUMEN

MOTIVATION: Studying ageing effects on molecules is an important new topic for life science. To perform such studies, the need for data, models, algorithms, and tools arises to elucidate molecular mechanisms. GTEx (standing for Genotype-Tissue Expression) portal is a web-based data source allowing to retrieve patients' transcriptomics data annotated with tissues, gender, and age information. It represents the more complete data sources for ageing effects studies. Nevertheless, it lacks functionalities to query data at the sex/age level, as well as tools for protein interaction studies, thereby limiting ageing studies. As a result, users need to download query results to proceed to further analysis, such as retrieving the expression of a given gene on different age (or sex) classes in many tissues. RESULTS: We present the GTExVisualizer, a platform to query and analyse GTEx data. This tool contains a web interface able to: (i) graphically represent and study query results; (ii) analyse genes using sex/age expression patterns, also integrated with network-based modules; and (iii) report results as plot-based representation as well as (gene) networks. Finally, it allows the user to obtain basic statistics which evidence differences in gene expression among sex/age groups. CONCLUSION: The GTExVisualizer novelty consists in providing a tool for studying ageing/sex-related effects on molecular processes. AVAILABILITY AND IMPLEMENTATION: GTExVisualizer is available at: http://gtexvisualizer.herokuapp.com. The source code and data are available at: https://github.com/UgoLomoio/gtex_visualizer.


Asunto(s)
Perfilación de la Expresión Génica , Programas Informáticos , Humanos , Algoritmos
3.
Cardiovasc Diabetol ; 23(1): 144, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38671460

RESUMEN

BACKGROUND: Evidence has shown that women with type 2 diabetes (T2DM) have a higher excess risk for cardiovascular disease (CVD) than men with T2DM. Subjects with either T2DM or prediabetes exhibit myocardial insulin resistance, but it is still unsettled whether sex-related differences in myocardial insulin resistance occur in diabetic and prediabetic subjects. METHODS: We aimed to evaluate sex-related differences in myocardial glucose metabolic rate (MRGlu), assessed using dynamic PET with 18F-FDG combined with euglycemic-hyperinsulinemic clamp, in subjects with normal glucose tolerance (NGT; n = 20), prediabetes (n = 11), and T2DM (n = 26). RESULTS: Women with prediabetes or T2DM exhibited greater relative differences in myocardial MRGlu than men with prediabetes or T2DM when compared with their NGT counterparts. As compared with women with NGT, those with prediabetes exhibited an age-adjusted 35% lower myocardial MRGlu value (P = 0.04) and women with T2DM a 74% lower value (P = 0.006), respectively. Conversely, as compared with men with NGT, men with T2DM exhibited a 40% lower myocardial MRGlu value (P = 0.004), while no significant difference was observed between men with NGT and prediabetes. The statistical test for interaction between sex and glucose tolerance on myocardial MRGlu (P < 0.0001) was significant suggesting a sex-specific association. CONCLUSIONS: Our data suggest that deterioration of glucose homeostasis in women is associated with a greater impairment in myocardial glucose metabolism as compared with men. The sex-specific myocardial insulin resistance could be an important factor responsible for the greater effect of T2DM on the excess risk of cardiovascular disease in women than in men.


Asunto(s)
Glucemia , Diabetes Mellitus Tipo 2 , Técnica de Clampeo de la Glucosa , Resistencia a la Insulina , Miocardio , Estado Prediabético , Humanos , Masculino , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Estado Prediabético/metabolismo , Estado Prediabético/diagnóstico , Estado Prediabético/epidemiología , Persona de Mediana Edad , Factores Sexuales , Miocardio/metabolismo , Glucemia/metabolismo , Adulto , Anciano , Biomarcadores/sangre , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones , Radiofármacos , Insulina/sangre , Estudios de Casos y Controles , Metabolismo Energético
4.
BMC Med Inform Decis Mak ; 24(1): 93, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38584282

RESUMEN

Proteomic-based analysis is used to identify biomarkers in blood samples and tissues. Data produced by devices such as mass spectrometry requires platforms to identify and quantify proteins (or peptides). Clinical information can be related to mass spectrometry data to identify diseases at an early stage. Machine learning techniques can be used to support physicians and biologists in studying and classifying pathologies. We present the application of machine learning techniques to define a pipeline aimed at studying and classifying proteomics data enriched using clinical information. The pipeline allows users to relate established blood biomarkers with clinical parameters and proteomics data. The proposed pipeline entails three main phases: (i) feature selection, (ii) models training, and (iii) models ensembling. We report the experience of applying such a pipeline to prostate-related diseases. Models have been trained on several biological datasets. We report experimental results about two datasets that result from the integration of clinical and mass spectrometry-based data in the contexts of serum and urine analysis. The pipeline receives input data from blood analytes, tissue samples, proteomic analysis, and urine biomarkers. It then trains different models for feature selection, classification and voting. The presented pipeline has been applied on two datasets obtained in a 2 years research project which aimed to extract hidden information from mass spectrometry, serum, and urine samples from hundreds of patients. We report results on analyzing prostate datasets serum with 143 samples, including 79 PCa and 84 BPH patients, and an urine dataset with 121 samples, including 67 PCa and 54 BPH patients. As results pipeline allowed to identify interesting peptides in the two datasets, 6 for the first one and 2 for the second one. The best model for both serum (AUC=0.87, Accuracy=0.83, F1=0.81, Sensitivity=0.84, Specificity=0.81) and urine (AUC=0.88, Accuracy=0.83, F1=0.83, Sensitivity=0.85, Specificity=0.80) datasets showed good predictive performances. We made the pipeline code available on GitHub and we are confident that it will be successfully adopted in similar clinical setups.


Asunto(s)
Hiperplasia Prostática , Neoplasias de la Próstata , Masculino , Humanos , Proteómica , Próstata , Neoplasias de la Próstata/diagnóstico , Aprendizaje Automático , Biomarcadores , Péptidos
5.
Brief Bioinform ; 22(2): 855-872, 2021 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-33592108

RESUMEN

MOTIVATION: The outbreak of novel severe acute respiratory syndrome coronavirus (SARS-CoV-2, also known as COVID-19) in Wuhan has attracted worldwide attention. SARS-CoV-2 causes severe inflammation, which can be fatal. Consequently, there has been a massive and rapid growth in research aimed at throwing light on the mechanisms of infection and the progression of the disease. With regard to this data science is playing a pivotal role in in silico analysis to gain insights into SARS-CoV-2 and the outbreak of COVID-19 in order to forecast, diagnose and come up with a drug to tackle the virus. The availability of large multiomics, radiological, bio-molecular and medical datasets requires the development of novel exploratory and predictive models, or the customisation of existing ones in order to fit the current problem. The high number of approaches generates the need for surveys to guide data scientists and medical practitioners in selecting the right tools to manage their clinical data. RESULTS: Focusing on data science methodologies, we conduct a detailed study on the state-of-the-art of works tackling the current pandemic scenario. We consider various current COVID-19 data analytic domains such as phylogenetic analysis, SARS-CoV-2 genome identification, protein structure prediction, host-viral protein interactomics, clinical imaging, epidemiological research and drug discovery. We highlight data types and instances, their generation pipelines and the data science models currently in use. The current study should give a detailed sketch of the road map towards handling COVID-19 like situations by leveraging data science experts in choosing the right tools. We also summarise our review focusing on prime challenges and possible future research directions. CONTACT: hguzzi@unicz.it, sroy01@cus.ac.in.


Asunto(s)
Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Ciencia de los Datos , Reposicionamiento de Medicamentos , COVID-19/patología , COVID-19/virología , Humanos , SARS-CoV-2/aislamiento & purificación
6.
Bioinformatics ; 38(17): 4235-4237, 2022 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-35799364

RESUMEN

MOTIVATION: Protein Contact Network (PCN) is a powerful method for analysing the structure and function of proteins, with a specific focus on disclosing the molecular features of allosteric regulation through the discovery of modular substructures. The importance of PCN analysis has been shown in many contexts, such as the analysis of SARS-CoV-2 Spike protein and its complexes with the Angiotensin Converting Enzyme 2 (ACE2) human receptors. Even if there exist many software tools implementing such methods, there is a growing need for the introduction of tools integrating existing approaches. RESULTS: We present PCN-Miner, a software tool implemented in the Python programming language, able to (i) import protein structures from the Protein Data Bank; (ii) generate the corresponding PCN; (iii) model, analyse and visualize PCNs and related protein structures by using a set of known algorithms and metrics. The PCN-Miner can cover a large set of applications: from clustering to embedding and subsequent analysis. AVAILABILITY AND IMPLEMENTATION: The PCN-Miner tool is freely available at the following GitHub repository: https://github.com/hguzzi/ProteinContactNetworks. It is also available in the Python Package Index (PyPI) repository.


Asunto(s)
Mapeo de Interacción de Proteínas , Proteínas , Humanos , Lenguajes de Programación , SARS-CoV-2 , Programas Informáticos
7.
Clin Proteomics ; 20(1): 52, 2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-37990292

RESUMEN

BACKGROUND: Prostate Cancer (PCa) represents the second leading cause of cancer-related death in men. Prostate-specific antigen (PSA) serum testing, currently used for PCa screening, lacks the necessary sensitivity and specificity. New non-invasive diagnostic tools able to discriminate tumoral from benign conditions and aggressive (AG-PCa) from indolent forms of PCa (NAG-PCa) are required to avoid unnecessary biopsies. METHODS: In this work, 32 formerly N-glycosylated peptides were quantified by PRM (parallel reaction monitoring) in 163 serum samples (79 from PCa patients and 84 from individuals affected by benign prostatic hyperplasia (BPH)) in two technical replicates. These potential biomarker candidates were prioritized through a multi-stage biomarker discovery pipeline articulated in: discovery, LC-PRM assay development and verification phases. Because of the well-established involvement of glycoproteins in cancer development and progression, the proteomic analysis was focused on glycoproteins enriched by TiO2 (titanium dioxide) strategy. RESULTS: Machine learning algorithms have been applied to the combined matrix comprising proteomic and clinical variables, resulting in a predictive model based on six proteomic variables (RNASE1, LAMP2, LUM, MASP1, NCAM1, GPLD1) and five clinical variables (prostate dimension, proPSA, free-PSA, total-PSA, free/total-PSA) able to distinguish PCa from BPH with an area under the Receiver Operating Characteristic (ROC) curve of 0.93. This model outperformed PSA alone which, on the same sample set, was able to discriminate PCa from BPH with an AUC of 0.79. To improve the clinical managing of PCa patients, an explorative small-scale analysis (79 samples) aimed at distinguishing AG-PCa from NAG-PCa was conducted. A predictor of PCa aggressiveness based on the combination of 7 proteomic variables (FCN3, LGALS3BP, AZU1, C6, LAMB1, CHL1, POSTN) and proPSA was developed (AUC of 0.69). CONCLUSIONS: To address the impelling need of more sensitive and specific serum diagnostic tests, a predictive model combining proteomic and clinical variables was developed. A preliminary evaluation to build a new tool able to discriminate aggressive presentations of PCa from tumors with benign behavior was exploited. This predictor displayed moderate performances, but no conclusions can be drawn due to the limited number of the sample cohort. Data are available via ProteomeXchange with identifier PXD035935.

8.
Cardiovasc Diabetol ; 22(1): 4, 2023 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-36624469

RESUMEN

BACKGROUND: Alterations in myocardial mechano-energetic efficiency (MEEi), which represents the capability of the left ventricles to convert the chemical energy obtained by oxidative metabolism into mechanical work, have been associated with cardiovascular disease. Although whole-body insulin resistance has been related to impaired myocardial MEEi, it is unknown the relationship between cardiac insulin resistance and MEEi. Aim of this study was to evaluate the relationship between insulin-stimulated myocardial glucose metabolic rate (MrGlu) and myocardial MEEi in subjects having different degrees of glucose tolerance. METHODS: We evaluated insulin-stimulated myocardial MrGlu using cardiac dynamic positron emission tomography (PET) with 18F-Fluorodeoxyglucose (18F-FDG) combined with euglycemic-hyperinsulinemic clamp, and myocardial MEEi in 57 individuals without history of coronary heart disease having different degrees of glucose tolerance. The subjects were stratified into tertiles according to their myocardial MrGlu values. RESULTS: After adjusting for age, gender and BMI, subjects in I tertile showed a decrease in myocardial MEEi (0.31 ± 0.05 vs 0.42 ± 0.14 ml/s*g, P = 0.02), and an increase in myocardial oxygen consumption (MVO2) (10,153 ± 1375 vs 7816 ± 1229 mmHg*bpm, P < 0.0001) as compared with subjects in III tertile. Univariate correlations showed that insulin-stimulated myocardial MrGlu was positively correlated with MEEi and whole-body glucose disposal, and negatively correlated with waist circumference, fasting plasma glucose, HbA1c and MVO2. In a multivariate regression analysis running a model including several CV risk factors, the only variable that remained significantly associated with MEEi was myocardial MrGlu (ß 0.346; P = 0.01). CONCLUSIONS: These data suggest that an impairment in insulin-stimulated myocardial glucose metabolism is an independent contributor of depressed myocardial MEEi in subjects without history of CHD.


Asunto(s)
Glucosa , Resistencia a la Insulina , Humanos , Glucosa/metabolismo , Insulina , Miocardio/metabolismo , Corazón , Fluorodesoxiglucosa F18/metabolismo
9.
BMC Bioinformatics ; 22(Suppl 15): 614, 2022 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-35012460

RESUMEN

BACKGROUND: Representations of the relationships among data using networks are widely used in several research fields such as computational biology, medical informatics and social network mining. Recently, complex networks have been introduced to better capture the insights of the modelled scenarios. Among others, dual networks (DNs) consist of mapping information as pairs of networks containing the same set of nodes but with different edges: one, called physical network, has unweighted edges, while the other, called conceptual network, has weighted edges. RESULTS: We focus on DNs and we propose a tool to find common subgraphs (aka communities) in DNs with particular properties. The tool, called Dual-Network-Analyser, is based on the identification of communities that induce optimal modular subgraphs in the conceptual network and connected subgraphs in the physical one. It includes the Louvain algorithm applied to the considered case. The Dual-Network-Analyser can be used to study DNs, to find common modular communities. We report results on using the tool to identify communities on synthetic DNs as well as real cases in social networks and biological data. CONCLUSION: The proposed method has been tested by using synthetic and biological networks. Results demonstrate that it is well able to detect meaningful information from DNs.


Asunto(s)
Algoritmos , Biología Computacional
10.
Diabetes Obes Metab ; 24(12): 2319-2330, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35837991

RESUMEN

AIM: To determine whether treatment with empagliflozin was able to affect the myocardial glucose metabolic rate, as assessed by cardiac dynamic 18 F-fluorodeoxyglucose-positron emission tomography (18 F-FDG-PET) combined with euglycaemic-hyperinsulinaemic clamp compared with glimepiride in patients with type 2 diabetes. MATERIALS AND METHODS: To further investigate the cardioprotective mechanism of sodium-glucose co-transporter-2 inhibitors, we performed a 26-week, randomized, open-label, crossover, active-comparator study to determine the effects of empagliflozin 10 mg versus glimepiride 2 mg daily on the myocardial glucose metabolic rate assessed by cardiac dynamic 18 F-FDG-PET combined with euglycaemic-hyperinsulinaemic clamp in 23 patients with type 2 diabetes. We also measured cardiac geometry and myocardial mechano-energetic efficiency, as well as systolic and diastolic function by echocardiography. RESULTS: Compared with glimepiride, treatment with empagliflozin resulted in a greater reduction in the myocardial glucose metabolic rate from baseline to 26 weeks (adjusted difference -6.07 [-8.59, -3.55] µmol/min/100 g; P < .0001). Moreover, compared with glimepiride, empagliflozin led to significant reductions in left atrial diameter, left ventricular end-systolic and end-diastolic volumes, N-terminal pro b-type natriuretic peptide levels, blood pressure, heart rate, stroke work, and myocardial oxygen consumption estimated by the rate pressure product, and increases in ejection fraction, myocardial mechano-energetic efficiency, red blood cells, and haematocrit and haemoglobin levels. CONCLUSIONS: The present study provides evidence that empagliflozin treatment in subjects with type 2 diabetes without coronary artery disease leads to a significant reduction in the myocardial glucose metabolic rate.


Asunto(s)
Diabetes Mellitus Tipo 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucosa , Fluorodesoxiglucosa F18 , Compuestos de Bencidrilo/uso terapéutico , Compuestos de Bencidrilo/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología
11.
Eur Heart J ; 41(45): 4332-4345, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-32330934

RESUMEN

AIMS: Cardiac myxomas usually develop in the atria and consist of an acid-mucopolysaccharide-rich myxoid matrix with polygonal stromal cells scattered throughout. These human benign tumours are a valuable research model because of the rarity of cardiac tumours, their clinical presentation and uncertain origin. Here, we assessed whether multipotent cardiac stem/progenitor cells (CSCs) give rise to atrial myxoma tissue. METHODS AND RESULTS: Twenty-three myxomas were collected and analysed for the presence of multipotent CSCs. We detected myxoma cells positive for c-kit (c-kitpos) but very rare Isl-1 positive cells. Most of the c-kitpos cells were blood lineage-committed CD45pos/CD31pos cells. However, c-kitpos/CD45neg/CD31neg cardiac myxoma cells expressed stemness and cardiac progenitor cell transcription factors. Approximately ≤10% of the c-kitpos/CD45neg/CD31neg myxoma cells also expressed calretinin, a characteristic of myxoma stromal cells. In vitro, the c-kitpos/CD45neg/CD31neg myxoma cells secrete chondroitin-6-sulfate and hyaluronic acid, which are the main components of gelatinous myxoma matrix in vivo. In vitro, c-kitpos/CD45neg/CD31neg myxoma cells have stem cell properties being clonogenic, self-renewing, and sphere forming while exhibiting an abortive cardiac differentiation potential. Myxoma-derived CSCs possess a mRNA and microRNA transcriptome overall similar to normal myocardium-derived c-kitpos/CD45neg/CD31negCSCs , yet showing a relatively small and relevant fraction of dysregulated mRNA/miRNAs (miR-126-3p and miR-335-5p, in particular). Importantly, myxoma-derived CSCs but not normal myocardium-derived CSCs, seed human myxoma tumours in xenograft's in immunodeficient NOD/SCID mice. CONCLUSION: Myxoma-derived c-kitpos/CD45neg/CD31neg CSCs fulfill the criteria expected of atrial myxoma-initiating stem cells. The transcriptome of these cells indicates that they belong to or are derived from the same lineage as the atrial multipotent c-kitpos/CD45neg/CD31neg CSCs. Taken together the data presented here suggest that human myxomas could be the first-described CSC-related human heart disease.


Asunto(s)
Neoplasias Cardíacas , Mixoma , Animales , Ratones , Ratones Endogámicos NOD , Ratones SCID , Células Madre
13.
BMC Bioinformatics ; 18(Suppl 6): 235, 2017 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-28617222

RESUMEN

BACKGROUND: Recently the study of the complex system of connections in neural systems, i.e. the connectome, has gained a central role in neurosciences. The modeling and analysis of connectomes are therefore a growing area. Here we focus on the representation of connectomes by using graph theory formalisms. Macroscopic human brain connectomes are usually derived from neuroimages; the analyzed brains are co-registered in the image domain and brought to a common anatomical space. An atlas is then applied in order to define anatomically meaningful regions that will serve as the nodes of the network - this process is referred to as parcellation. The atlas-based parcellations present some known limitations in cases of early brain development and abnormal anatomy. Consequently, it has been recently proposed to perform atlas-free random brain parcellation into nodes and align brains in the network space instead of the anatomical image space, as a way to deal with the unknown correspondences of the parcels. Such process requires modeling of the brain using graph theory and the subsequent comparison of the structure of graphs. The latter step may be modeled as a network alignment (NA) problem. RESULTS: In this work, we first define the problem formally, then we test six existing state of the art of network aligners on diffusion MRI-derived brain networks. We compare the performances of algorithms by assessing six topological measures. We also evaluated the robustness of algorithms to alterations of the dataset. CONCLUSION: The results confirm that NA algorithms may be applied in cases of atlas-free parcellation for a fully network-driven comparison of connectomes. The analysis shows MAGNA++ is the best global alignment algorithm. The paper presented a new analysis methodology that uses network alignment for validating atlas-free parcellation brain connectomes. The methodology has been experimented on several brain datasets.


Asunto(s)
Algoritmos , Encéfalo/diagnóstico por imagen , Conectoma/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Humanos , Imagen por Resonancia Magnética/métodos
14.
Opt Express ; 24(2): A180-90, 2016 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-26832572

RESUMEN

In this work a Raman flow cytometer is presented. It consists of a microfluidic device that takes advantages of the basic principles of Raman spectroscopy and flow cytometry. The microfluidic device integrates calibrated microfluidic channels- where the cells can flow one-by-one -, allowing single cell Raman analysis. The microfluidic channel integrates plasmonic nanodimers in a fluidic trapping region. In this way it is possible to perform Enhanced Raman Spectroscopy on single cell. These allow a label-free analysis, providing information about the biochemical content of membrane and cytoplasm of the each cell. Experiments are performed on red blood cells (RBCs), peripheral blood lymphocytes (PBLs) and myelogenous leukemia tumor cells (K562).


Asunto(s)
Dimerización , Técnicas Analíticas Microfluídicas/instrumentación , Nanopartículas/química , Análisis de la Célula Individual/instrumentación , Espectrometría Raman/instrumentación , Humanos , Células K562 , Fenómenos Ópticos
15.
BMC Bioinformatics ; 15: 6, 2014 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-24410833

RESUMEN

BACKGROUND: Protein inter-residue contact maps provide a translation and rotation invariant topological representation of a protein. They can be used as an intermediary step in protein structure predictions. However, the prediction of contact maps represents an unbalanced problem as far fewer examples of contacts than non-contacts exist in a protein structure.In this study we explore the possibility of completely eliminating the unbalanced nature of the contact map prediction problem by predicting real-value distances between residues. Predicting full inter-residue distance maps and applying them in protein structure predictions has been relatively unexplored in the past. RESULTS: We initially demonstrate that the use of native-like distance maps is able to reproduce 3D structures almost identical to the targets, giving an average RMSD of 0.5Å. In addition, the corrupted physical maps with an introduced random error of ±6Å are able to reconstruct the targets within an average RMSD of 2Å.After demonstrating the reconstruction potential of distance maps, we develop two classes of predictors using two-dimensional recursive neural networks: an ab initio predictor that relies only on the protein sequence and evolutionary information, and a template-based predictor in which additional structural homology information is provided. We find that the ab initio predictor is able to reproduce distances with an RMSD of 6Å, regardless of the evolutionary content provided. Furthermore, we show that the template-based predictor exploits both sequence and structure information even in cases of dubious homology and outperforms the best template hit with a clear margin of up to 3.7Å.Lastly, we demonstrate the ability of the two predictors to reconstruct the CASP9 targets shorter than 200 residues producing the results similar to the state of the machine learning art approach implemented in the Distill server. CONCLUSIONS: The methodology presented here, if complemented by more complex reconstruction protocols, can represent a possible path to improve machine learning algorithms for 3D protein structure prediction. Moreover, it can be used as an intermediary step in protein structure predictions either on its own or complemented by NMR restraints.


Asunto(s)
Biología Computacional/métodos , Modelos Moleculares , Redes Neurales de la Computación , Proteínas/química , Algoritmos , Bases de Datos de Proteínas , Conformación Proteica , Análisis de Secuencia de Proteína
16.
Hum Brain Mapp ; 35(7): 3122-31, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24142480

RESUMEN

To test a prediction of our previous computational model of cortico-hippocampal interaction (Gluck and Myers [1993, 2001]) for characterizing individual differences in category learning, we studied young healthy subjects using an fMRI-adapted category-learning task that has two phases, an initial phase in which associations are learned through trial-and-error feedback followed by a generalization phase in which previously learned rules can be applied to novel associations (Myers et al. [2003]). As expected by our model, we found a negative correlation between learning-related hippocampal responses and accuracy during transfer, demonstrating that hippocampal adaptation during learning is associated with better behavioral scores during transfer generalization. In addition, we found an inverse relationship between Blood Oxygenation Level Dependent (BOLD) activity in the striatum and that in the hippocampal formation and the orbitofrontal cortex during the initial learning phase. Conversely, activity in the dorsolateral prefrontal cortex, orbitofrontal cortex and parietal lobes dominated over that of the hippocampal formation during the generalization phase. These findings provide evidence in support of theories of the neural substrates of category learning which argue that the hippocampal region plays a critical role during learning for appropriately encoding and representing newly learned information so that that this learning can be successfully applied and generalized to subsequent novel task demands.


Asunto(s)
Discriminación en Psicología/fisiología , Generalización Psicológica/fisiología , Hipocampo/irrigación sanguínea , Transferencia de Experiencia en Psicología/fisiología , Adulto , Femenino , Hipocampo/fisiología , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Oxígeno/sangre , Valor Predictivo de las Pruebas , Tiempo de Reacción , Adulto Joven
17.
Stud Health Technol Inform ; 314: 103-107, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38785012

RESUMEN

The Prediabetes impacts one in every three individuals, with a 10% annual probability of transitioning to type 2 diabetes without lifestyle changes or medical interventions. It's crucial to manage glycemic health to deter the progression to type 2 diabetes. In the United States, 13% of individuals (18 years of age and older) have diabetes, while 34.5% meet the criteria for prediabetes. Diabetes mellitus and prediabetes are more common in older persons. Currently, nevertheless, there aren't many noninvasive, commercially accessible methods for tracking glycemic status to help with prediabetes self-management. This study tackles the task of forecasting glucose levels using personalized prediabetes data through the utilization of the Long Short-Term Memory (LSTM) model. Continuous monitoring of interstitial glucose levels, heart rate measurements, and dietary records spanning a week were collected for analysis. The efficacy of the proposed model has been assessed using evaluation metrics including Root Mean Square Error (RMSE), Mean Squared Error (MSE), Mean Absolute Error (MAE), and the coefficient of determination (R2).


Asunto(s)
Glucemia , Diabetes Mellitus Tipo 2 , Estado Prediabético , Humanos , Estado Prediabético/sangre , Diabetes Mellitus Tipo 2/sangre , Glucemia/análisis , Automonitorización de la Glucosa Sanguínea , Masculino , Redes Neurales de la Computación
18.
Stud Health Technol Inform ; 314: 187-191, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38785029

RESUMEN

The evolution of socio-technological habits together with the widespread demand of post-acute and chronic treatments outside hospital boundaries drove the increased demand of medical informatics experts to develop tools for and support healthcare professionals. The recent COVID-19 pandemic further highlighted the need of physicians able to manage diseases virtually and remotely. Moreover, healthcare professionals need to access to innovative techniques and procedures to manage biomedical data, cloud-based communication, and data sharing procedures, often connected to innovative devices to support an effective precision in the health treatments. In this paper we report the experiences of the Italian Biomedical Informatics Society (SIBIM), in the definition and promotion of eHealth educational topics in medical and health professions teaching programs, as well as in bioengineering schools, showing how SIBIM members' efforts have been applied towards increasing the level of eHealth contents in medical schools.


Asunto(s)
Informática Médica , Italia , Informática Médica/educación , COVID-19 , Humanos , Curriculum , Sociedades Médicas , Telemedicina , SARS-CoV-2
19.
Sci Rep ; 14(1): 12548, 2024 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-38822012

RESUMEN

Patient triage is crucial in emergency departments, ensuring timely and appropriate care based on correctly evaluating the emergency grade of patient conditions. Triage methods are generally performed by human operator based on her own experience and information that are gathered from the patient management process. Thus, it is a process that can generate errors in emergency-level associations. Recently, Traditional triage methods heavily rely on human decisions, which can be subjective and prone to errors. A growing interest has recently been focused on leveraging artificial intelligence (AI) to develop algorithms to maximize information gathering and minimize errors in patient triage processing. We define and implement an AI-based module to manage patients' emergency code assignments in emergency departments. It uses historical data from the emergency department to train the medical decision-making process. Data containing relevant patient information, such as vital signs, symptoms, and medical history, accurately classify patients into triage categories. Experimental results demonstrate that the proposed algorithm achieved high accuracy outperforming traditional triage methods. By using the proposed method, we claim that healthcare professionals can predict severity index to guide patient management processing and resource allocation.


Asunto(s)
Algoritmos , Servicio de Urgencia en Hospital , Redes Neurales de la Computación , Triaje , Triaje/métodos , Humanos , Inteligencia Artificial , Toma de Decisiones Clínicas/métodos
20.
Stud Health Technol Inform ; 314: 168-172, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38785025

RESUMEN

Telemonitoring tools have become essential in today's healthcare, representing fundamental resources for chronic disease home management supporting early detection of clinical worsening with great reduction of hospitalization costs. Therefore the investigation of the patient compliance is a key enabling point. We aim to assess how patients with chronic coronary syndromes evaluate a telemonitoring device meant for ongoing health monitoring. Twenty-six patients used the device for a week and subsequently filled out a well-designed questionnaire. The survey questions were about the device's ease of use, satisfaction levels, perceived effectiveness, and its influence on the patients' healthcare experiences. This study emphasizes the significance of focusing on patient needs in telemedicine and the importance of addressing these concerns to improve telehealth interventions.


Asunto(s)
Satisfacción del Paciente , Medicina de Precisión , Telemedicina , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Encuestas y Cuestionarios , Cooperación del Paciente
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