Biology subjects

Lemos, B.

Publications and source records attributed to Lemos, B..

7 recordsLinked to original sources

bioRxiv2025

Brain Stroke Prediction: A PSO Optimized Stacked Ensemble Machine Learning Approach with SMOTEEN Data Balancing

Prediction of stroke is a critical challenge in healthcare, where early intervention can significantly reduce risks and improve patient outcomes. Traditional methods often struggle with imbalanced datasets and low prediction accuracy. This paper proposes a novel approach to address these issues by combining PSO-optimized Stacked Ensemble ML Classifiers with SMOTEEN data balancing to predict strokes effectively. The technique optimizes 3 Baseline ML Classifiers(RF, SVM, XGB) using Particle Swarm Optimization (PSO) and Stacked Ensemble approach is applied that significantly improving prediction performance. The proposed methodology achieved an impressive 95.57% accuracy, outperforming conventional models such as SVM, LR, RF, KNN, XGB. Overall, the PSO-optimized stacked ensemble approach outperforms traditional machine learning techniques in stroke prediction, providing a more accurate and robust model for early detection and intervention.

bioengineering↗

bioRxiv2025

Explainable AI-Driven Diagnosis Model for Early Glaucoma Detection Using Grey-Wolf Optimized Extreme Learning Machine Approach

Glaucoma is a prominent threat to vision and ranks as the third leading cause of blindness in India. Early detection is crucial to limit its progression. Retinal image analysis, particularly computer-aided diagnosis (CAD), has gained significant attention due to its potential in effectively screening for and managing glaucoma. Nowadays, Artificial intelligence (AI) has achieved significant progress has been made in medical image analysis across various applications. However, the main challenge hindering the widespread adoption of deep neural models in clinical settings is their lack of interpretability. In response to this need, we propose an enhanced CAD model with four key components: image pre-processing, feature extraction, feature dimensionality reduction, and classification. Utilizing the G1020 and ORIGA datasets, we employ a fast discrete curvelet transform with wrapping (FDCT-WRP) for curve-like feature extraction. A combined feature reduction technique, principal component analysis (PCA) and linear discriminant analysis (LDA), is applied to generate relevant features and reduce the feature dimensionality. Incorporating an improved grey wolf Optimization (IMGWO) with an Extreme Learning Machine (ELM) for classification. Then, IMGWO optimizes parameters, enhancing the efficiency of single-hidden-layer feedforward neural networks. Through a 10 x 5-fold stratified cross-validation (SCV) test on standard datasets, our CAD model demonstrates superior performance. The proposed CAD model achieved better classification result i.e., 93.87% and 95.38% on the G1020 and ORIGA datasets respectively. Additionally, we have proposed a framework named as GlaucoXAI (Glaucoma explainable artificial intelligence), which utilizes seven advanced explanation methods to improve the interpretability of deep learning models for medical experts trust. GlaucoXAI has been employed on glaucoma detection using fundus images. GlaucoXAIs adaptable design could aid ophthalmologists and medical professionals in detection of glaucoma. The experimental results demonstrate that the proposed model surpasses other existing models in classification accuracy, while significantly reducing the number of features.

bioengineering↗

bioRxiv2020

Chromosome structure due to phospho-mimetic H2A modulates DDR through increased chromatin mobility

In budding yeast and mammals, double strand breaks trigger global chromatin mobility together with the rapid phosphorylation of the histone H2A over an extensive region of the chromatin. To assess the role of H2A phosphorylation in this response to DNA damage, we have constructed strains where H2A has been mutated to the phospho-mimetic H2A-S129E. We show that H2A-S129E mutant increases global motion of chromosomes even in the absence of DNA damage. The intrinsic chromatin mobility of H2A-S129E is not due to checkpoint activation, histone degradation or kinetochore anchoring. Rather, the increased intra-chromosomal distances observed in H2A-S129E mutant are consistent with chromatin structural changes. In this context, the Rad953BP1-dependent-checkpoint becomes dispensable. The increase in chromatin dynamics is favorable to NHEJ of a single double-strand break but is accompanied by a sharp decrease in inter-chromosomal translocation rates. We propose that changes in chromosomal conformation due to H2A phosphorylation are sufficient to modulate the DDR and maintain genome integrity.

genetics↗

bioRxiv2019

Yeast Securin is trafficked through the endomembrane system to regulate cell cycle arrest during the DNA damage response

The yeast securin protein, Pds1, belongs to a class of highly conserved eukaryotic proteins that regulate the timing of chromatid segregation during mitosis by inhibiting separase, Esp1. During the metaphase to anaphase transition Pds1 is degraded by the ubiquitin-proteasome system in the nucleus, unleashing Esp1s protease activity to cleave cohesin surrounding sister chromatids. In response to DNA damage Pds1 is phosphorylated and stabilized, stalling mitotic progression to preserve genomic integrity. In addition, during the DNA damage checkpoint response, securin and separase are partially localized in the vacuole. Here we genetically dissect the requirements for securins vacuolar localization and find that it is dependent on the Alkaline Phosphatase (ALP) endosomal transport pathway but not autophagy. Blocking retrograde traffic between the Golgi and the endoplasmic reticulum, by inhibiting COPI vesicle transport, drives Pds1 into the vacuole, whereas inhibiting antegrade transport by disrupting COPII-mediated traffic, results in the unexpected loss of Pds1 and the extinction of DNA damage-induced cell cycle arrest. We report that the induction of ER stress, either genetically or by treating cells with dithiothreitol, is sufficient to extinguish the DNA damage checkpoint, suggesting crosstalk between these two pathways. These data highlight new ways in which Pds1 and Esp1 are regulated during a DNA damage induced G2/M arrest and its requirement in the maintenance of the DNA damage checkpoint response.

cell biology↗

bioRxiv2019

CImP: Cellular Imprinting Proteomics applied to ocular disorders elicited by Congenital Zika virus Syndrome

IMPORTANCEOcular complications in infants with Congenital Zika Syndrome (CZS) have been reported. However, the molecular mechanisms underlying of eye dysfunctions are presently unknown.\n\nOBJECTIVEA method (termed Cellular Imprinting Proteomics, CImP) for the identification and quantification of the ocular surface proteome using a minimally invasive membrane filter device is described. Moreover, The CImP method was applied to profile the molecular alterations in the eyes of infants exposed to Zika virus (ZIKV) infection during gestation.\n\nDESIGN, SETTINGS AND PARTICIMPANTSThe CImP method was applied to a cohort divided into three conditions: 1) Ctrl (infants with no infectious diseases, n=5). 2) Zikv (infants exposed to ZIKV gestation, with no microcephaly, n=5). 3) ZikvCZS (infants exposed to ZIKV, with microcephaly, n=3). All conditions were age and sex-matched. An improved impression cytology method was used to capture the outermost ocular surface cells. The number of impression cytology membrane collected was: Ctrl (12), Zikv (14) and ZikvCZS (8). Proteins were extracted and analysed using mass spectrometry-based proteomics technology followed by statistical analysis. Parallel reaction monitoring was performed to validate the expression of specific protein markers.\n\nRESULTSUsing the CImP method, 2209 proteins were identified on the membrane-captured conjunctiva epithelial cells. Modulation of neutrophil degranulation, cell death, ocular and neurodevelopment pathways are reported in infants with CZS compared to matched controls. Moreover, the molecular pattern of ocular surface cells retrieved from infants infected during the gestation but with no CZS was different from matched controls.\n\nCONCLUSIONS AND PERSPECTIVESMolecular alterations in the ocular cell surface associated to ZIKV infection with and without CZS complications are reported for the first time. We predict that this method will be introduced successfully in the study of several neurological diseases with the aim to identify novel diagnostic and therapeutic biomarkers.

biochemistry↗

bioRxiv2019

Impression cytology is a non-invasive and effective method for ocular cell obtention from babies with Congenital Zika Syndrome: perspectives in OMIC studies.

IMPORTANCENoninvasive techniques for obtaining ocular surface cells (neuroepithelial) from babies with Congenital Zika Syndrome CZS - resulting from infection by zika virus (ZIKV) during gestational period (malformations include ocular abnormalities and microcephaly) - remain to be determined.\n\nOBJECTIVESThe aim of this study was to describe an optimized impression cytology method for the isolation of viable cells from babies with CZS in satisfactory amounts and quality to enable the application in the context of genome approaches well as morphological and molecular evaluations.\n\nDESIGN, SETTINGS AND PARTICIPANTSIn this observational study, ocular surface samples were obtained with a hydrophilic nitrocellulose membrane (through optimized impression cytology method) from twelve babies referred to the Pediatric Service of the Antonio Pedro Hospital, Universidade Federal Fluminense (UFF), Niteroi, Rio de Janeiro, Brazil. Samples were collected with an authorized informed consent from both eyes of eight ZIKV infected babies according to the CZS diagnostic criteria (4 babies with positive PCR for Zika virus in gestation and presence of clinical signs which included ocular abnormalities and microcephaly and 4 babies with positive PCR for Zika virus during gestation but no clinical signs identified) and four unaffected babies (control samples / negative PCR, without clinical signs). Cells were used for microscopy analyses, transcriptomic and proteomic experiments and molecular procedure.\n\nMAIN OUTCOMES AND MEASURESThe microscopic features of the conjunctival epithelial cells were described by both direct analysis of the membrane-attached cells and analysis of cytospinned captured cells using several staining procedures, including viability evaluation. In parallel, molecular approaches were performed.\n\nRESULTSOn impression cytology, a considerable amount of viable cells were captured. Epithelial basal, polyhedral and goblet cells were clearly identified in all groups. All cases of ZIKV infected babies showed clear morphological alterations (cell keratinization, piknosis, karyolysis, anucleation and vacuolization). Genomic DNA and RNA were successfully isolated from all samples and allowed the establishment of transcriptomic and proteomic studies. Transcriptome analysis showed 8582 transcripts quantified in all samples and 63 differentially expressed genes in ocular cells from the exposed babies. Proteomics analysis allowed the identification of 2080, 2085 and 2086 high confident and unique proteins with at least one unique peptide in the unaffected, exposed to ZIKV and asymptomatic and CZS babies, respectively, being 2062 in common. Multivariate supervised analysis using the total quantitative protein features revealed a clear discrimination between the groups.\n\nCONCLUSIONS AND RELEVANCEOur method proved to be a suitable, fast, and non-invasive tool for detailed and precise morphological analyses with a perspective of application in OMIC studies for clinical and research studies of CZS.\n\nKey pointsO_ST_ABSQuestionC_ST_ABSAre the ocular surface cells of babies with Congenital Zika Syndrome viable to investigate the association between Zika virus infection during embryogenesis and ocular impairment?\n\nFindingsTo this date, this is the first study using an approach with perspectives in morphological, molecular and \"OMICs\" research from ocular samples captured by impression cytology of ZIKV infected babies during embryogenesis. The microscopic features of the conjunctival epithelial cells from all ZIKV infected babies showed clear morphological alterations.\n\nMeaningOcular cell surface capture offers a powerful model for studying the pathways involved in ocular diseases associated with ZIKV.

molecular biology↗

bioRxiv2017

Genetic context and proliferation determine contrasting patterns of copy number amplification and loss for 5S and 45S ribosomal DNA arrays in cancer

The multicopy 45S ribosomal DNA (45S rDNA) array gives origin to the nucleolus, the first discovered nuclear organelle, site of Poll I 45S rRNA transcription and key regulator of cellular metabolism, DNA repair response, genome stability, and global epigenetic states. The multicopy 5S ribosomal DNA array (5S rDNA) is located on a separate chromosome, encodes the 5S rRNA transcribed by Pol III, and exhibits concerted copy number variation (cCNV) with the 45S rDNA array in human blood. Here we combined genomic data from >700 tumors and normal tissues to provide a portrait of ribosomal DNA variation in human tissues and cancers of diverse mutational signatures. We show that most cancers undergo coupled 5S rDNA array amplification and 45S rDNA loss, with abundant inter-individual variation in rDNA copy number of both arrays, and concerted modulation of 5S-45S copy number in some but not all tissues. Analysis of genetic context revealed associations between the presence of specific somatic alterations, such as P53 mutations in stomach and lung adenocarcinomas, and coupled 5S gain / 45S loss. Finally, we show that increased proliferation rates along cancer lineages can partially explain contrasting copy number changes in the 5S and 45S rDNA arrays. We suggest that 5S rDNA amplification facilitates increased ribosomal synthesis in cancer, whereas 45S rDNA loss emerges as a byproduct of transcription-replication conflict in highly proliferating tumor cells. Our results highlight the tissue- specificity of concerted copy number variation and uncover contrasting changes in 5S and 45S rDNA copy number along rapidly proliferating cell lineages.\n\nLay SummaryThe 45S and 5S ribosomal DNA (rDNA) arrays contain hundreds of rDNA copies, with substantial variability across individuals and species. Although physically unlinked, both arrays exhibit concerted copy number variation. However, whether concerted copy number is universally observed across all tissues is unknown. It also remains unknown if rDNA copy number may vary in tissues and cancer lineages. Here we showed that most cancers undergo coupled 5S rDNA array amplification and 45S rDNA loss, and concerted 5S-45S copy number variation in some but not all tissues. The coupled 5S amplification and 45S loss is associated with the presence of certain somatic genetic variations, as well as increased cancerous cell proliferation rate. Our research highlights the tissue- specificity of concerted copy number variation and uncover contrasting changes in rDNA copy number along rapidly proliferating cell lineages. Our observations raise the prospects of using 5S and 45S ribosomal DNA states as indicators of cancer status and targets in new strategies for cancer therapy.

genomics↗