Biology subjects

Cordeiro, D.

Publications and source records attributed to Cordeiro, D..

4 recordsLinked to original sources

bioRxiv2025

GARN3: A coarse-grained helix centered technique for RNA 3D structures prediction

The study of the prediction of three-dimensional structures of RNA (ribonucleic acids) has been increasing over the last decades, especially with advances in artificial intelligence. However, there are still many gaps. Among the known techniques, GARN (Game Algorithms for RNa 3D sampling) has demonstrated good results in molecules with long structures containing hundreds of millions of nucleotides. Nevertheless, the GARN technique also left room for improvements when considering its final 3D structure for predicted molecules, which can be more refined by presenting more elements, also known as pseudoatoms. In this study, we improved the last version of the technique GARN, which is GARN2, enhancing the visualization of the 3D model by adding more pseudoatoms to the helices in our technique GARN3. In GARN3, we also added a machine learning prediction model to improve the scoring calculation, aiming to improve the prediction of new molecules. In our tests, we demonstrated good results when comparing GARN3 with other techniques in the literature. GARN3, in the same way as GARN2, presents better results for large molecules. In our tests, the simulations with GARN3 demonstrated good results, where GARN3 predicted the majority of molecules (approximately 80% of the test set) better than the older versions of GARN.

bioinformatics↗

bioRxiv2023

Synaptic dysfunction and dysregulation of extracellular matrix-related genes in dopaminergic neurons derived from Parkinson's disease sporadic patients and with GBA1 mutations

Parkinsons disease (PD) is a neurodegenerative disease with both genetic and sporadic origins. In this study, we investigated the electrophysiological properties, synaptic activity, and gene expression differences in dopaminergic (DA) neurons derived from induced pluripotent stem cells (iPSCs) of healthy controls, sporadic PD (sPD) patients, and PD patients with GBA1 mutations. Our results demonstrate reduced sodium currents and synaptic activity in DA neurons derived from PD patients with GBA1 mutations, suggesting a potential contribution to PD pathophysiology. We also observed distinct electrophysiological alterations in sPD DA neurons that were dependent on the age of disease onset. RNA sequencing analysis revealed unique dysregulated pathways in early and late-onset sPD neurons, further supporting the notion that molecular mechanisms driving PD may be different between PD patients. In agreement with our previous reports, ECM and focal adhesion genes were the top dysregulated pathways in DA neurons from sPD patients and from patients with GBA1 mutations. Overall, this study gives further confirmation that the convergent functional phenotypes of DA neurons derived from PD patients are synaptic abnormalities and at the transcriptome level, ECM and focal adhesion pathways are highly involved in PD pathology across multiple PD-associated mutations as well as sPD.

neuroscience↗

bioRxiv2022

Monozygotic twins discordant for schizophrenia differ in maturation and synaptic transmission

Schizophrenia affects approximately 1% of the world population. Genetics, epigenetics, and environmental factors are known to play a role in this psychiatric disorder. While there is a high concordance in monozygotic twins, about half of twin pairs are discordant for schizophrenia. We characterized human-induced pluripotent stem cell (iPSC)-derived hippocampal neurons from two pairs of monozygotic twins that are discordant for a schizophrenia diagnosis. We compared the affected and the non-affected siblings and compared all of them to twin sets where none of the siblings suffered from schizophrenia. We found that the neurons derived from the schizophrenia patients were less arborized, were hypoexcitable with immature spike features, and exhibited a significant reduction in synaptic activity with dysregulation in synapse-related genes. Interestingly, the neurons derived from the co-twin siblings who did not have schizophrenia formed another distinct group that was different from the neurons in the group of the affected twin siblings but also different from the neurons in the group of the control twins. The neurons in the unaffected co-twin group were also less arborized than the neurons from controls but more arborized than those from affected siblings. Some of their spike features were immature (but less immature than neurons derived from the affected siblings). Importantly, their synaptic activity was not affected. Since schizophrenia is a genetically complex disorder, our twin study allows the measurement of neuronal phenotypes with a similar genetic background. The differences between the siblings may arise due to changes that occurred after the split of the egg into twins. Therefore, our study confirms that dysregulation of synaptic pathways, as well as changes in the rate of synaptic events, distinguishes between individuals affected with schizophrenia and unaffected individuals, even in those having a very similar genetic background.

neuroscience↗

bioRxiv2019

Chlamydia trachomatis outbreak: when the virulence-associated genome backbone imports a prevalence-associated major antigen signature

Chlamydia trachomatis is the most prevalent sexually transmitted bacteria worldwide and the causative agent of blinding trachoma. Strains are classified based on ompA genotypes, which are strongly linked with differential tissue tropism and disease outcomes. A lymphogranuloma venereum (LGV) epidemics, characterized by ulcerative proctitis, has emerged in the last two decades (mainly L2b genotype), raising high concern especially due to its circulation among men who have sex with men (MSM). Here, we report an ongoing outbreak (mostly affecting HIV-positive MSM engaging in high-risk practices) caused by an L2b strain with a rather unique genome makeup that precluded the laboratory notification of this outbreak as LGV due to its non-LGV ompA signature. Homologous recombination mediated the transfer of a ~4.5Kbp fragment enrolling CT681/ompA and neighboring genes (CT677/rrf, CT678/pyrH, CT679/tsf, CT680/rpsB) from a serovar D/Da strain likely possessing the typical T1 clade genome backbone associated with most prevalent genotypes (E and F). The hybrid L2b/D-Da strain presents the adhesin and immunodominant antigen MOMP (coded by ompA) with an epitope repertoire typical of non-invasive genital strains, while keeping the genome-dispersed virulence fingerprint of a classical LGV (L2b) strain. As previously reported for inter-clade ompA exchange among non-LGV clades, this unprecedented C. trachomatis genomic mosaic involving a contemporary epidemiologically and clinically relevant LGV strain may have implications on its transmission, tissue tropism and pathogenic capabilities. The emergence of such variants with epidemic and pathogenic potential highlights the need of more oriented surveillance strategies focused on capturing the C. trachomatis evolution in action.

genomics↗