Biology subjects

Garcia, F.

Publications and source records attributed to Garcia, F..

22 records · Page 2Linked to original sources

bioRxiv2021

From partial to whole genome imputation of SARS-CoV-2 for epidemiological surveillance

Backgroundthe current SARS-CoV-2 pandemic has emphasized the utility of viral whole genome sequencing in the surveillance and control of the pathogen. An unprecedented ongoing global initiative is increasingly producing hundreds of thousands of sequences worldwide. However, the complex circumstances in which viruses are sequenced, along with the demand of urgent results, causes a high rate of incomplete and therefore useless, sequences. However, viral sequences evolve in the context of a complex phylogeny and therefore different positions along the genome are in linkage disequilibrium. Therefore, an imputation method would be able to predict missing positions from the available sequencing data. ResultsWe developed impuSARS, an application that includes Minimac, the most widely used strategy for genomic data imputation and, taking advantage of the enormous amount of SARS-CoV-2 whole genome sequences available, a reference panel containing 239,301 sequences was built. The impuSARS application was tested in a wide range of conditions (continuous fragments, amplicons or sparse individual positions missing) showing great fidelity when reconstructing the original sequences. The impuSARS application is also able to impute whole genomes from commercial kits covering less than 20% of the genome or only from the Spike protein with a precision of 0.96. It also recovers the lineage with a 100% precision for almost all the lineages, even in very poorly covered genomes (< 20%) Conclusionsimputation can improve the pace of SARS-CoV-2 sequencing production by recovering many incomplete or low-quality sequences that would be otherwise discarded. impuSARS can be incorporated in any primary data processing pipeline for SARS-CoV-2 whole genome sequencing.

genomics↗

bioRxiv2020

PrimPol primase mediates replication traverse of DNA interstrand crosslinks

Interstrand crosslinks (ICLs) are DNA lesions frequently induced by chemotherapy that interfere with essential processes such as replication and transcription. ICL repair may be initiated by the convergence of two replication forks at the crosslink, which results in a termination-like DNA structure recognized and processed by the Fanconi Anemia (FA) pathway. An alternative possibility to generate a suitable substrate for ICL repair involves "ICL traverse", a DNA damage tolerance mechanism in which a single fork arriving at the ICL can skip the lesion and restart DNA synthesis from a downstream point. This reaction requires FANCM translocase, the BLM/TOP3A/RMI1-2 (BTR) complex and other factors. Here we report that PrimPol, the second primase-polymerase identified in mammalian cells after Pol/Primase, interacts with BTR and participates in the ICL traverse reaction. A functional complementation assay reveals that the primase activity of PrimPol is required, confirming the need for re-priming events during ICL traverse. Genetic ablation of PRIMPOL strongly impaired this tolerance mechanism, making cells more dependent on fork convergence to initiate ICL repair. PRIMPOL KO cells and mice display hypersensitivity to ICL-inducing drugs, opening the possibility of targeting PrimPol activity to enhance the efficacy of chemotherapy based on DNA crosslinking agents.

molecular biology↗

bioRxiv2020

A first Pseudomonas aeruginosa perturbome: Identification of core genes related to multiple perturbations by a machine learning approach

Tolerance to stress conditions is vital for organismal survival, including bacteria under specific environmental conditions, antibiotics, and other perturbations. Some studies have described common modulation and shared genes during stress response to different types of disturbances (termed as perturbome), leading to the idea of central control at the molecular level. We implemented a robust machine learning approach to identify and describe genes associated with multiple perturbations or perturbome in a Pseudomonas aeruginosa PAO1 model. Using microarray datasets from the Gene Expression Omnibus (GEO), we evaluated six approaches to rank and select genes: using two methodologies, data single partition (SP method) or multiple partitions (MP method) for training and testing datasets, we evaluated three classification algorithms (SVM Support Vector Machine, KNN K-Nearest neighbor and RF Random Forest). Gene expression patterns and topological features at the systems level were included to describe the perturbome elements. We were able to select and describe 46 core response genes associated with multiple perturbations in P. aeruginosa PAO1 and it can be considered a first report of the P. aeruginosa perturbome. Molecular annotations, patterns in expression levels, and topological features in molecular networks revealed biological functions of biosynthesis, binding, and metabolism, many of them related to DNA damage repair and aerobic respiration in the context of tolerance to stress. We also discuss different issues related to implemented and assessed algorithms, including data partitioning, classification approaches, and metrics. Altogether, this work offers a different and robust framework to select genes using a machine learning approach.

bioinformatics↗

bioRxiv2019

Overt and covert paths for sound in the auditory system of mammals

Current scientific consensus holds that sound is transmitted, solely mechanically, from the tympanum to the cochlea via ossicles.\n\nBut this theory does not explain the hearing extreme quality regarding high frequencies in mammals. So, we propose a bioelectronic pathway (the covert path) that is complementary to the overt path.\n\nWe demonstrate experimentally that the tympanum produces piezoelectric potentials isochronous to acoustic vibrations thanks to its collagen fibers and that their amplitude increases along with the frequency and level of the vibrations. This finding supports the existence of an electrical pathway, specialized in transmitting high-frequency sounds, that works in unison with the mechanical pathway. A bio-organic triode, similar to a field effect transistor, is the key mechanism of our hypothesized pathway. We present evidence that any deficiency along this pathway produces hearing impairment. By augmenting the classical theory of sound transmission, our discovery offers new perspectives for research into both normal and pathological audition and may contribute to an understanding of genetic and physiological problems of hearing.

physiology↗