Biology subjects

Lopez-Rincon, A.

Publications and source records attributed to Lopez-Rincon, A..

5 recordsLinked to original sources

bioRxiv2022

SARS-CoV-2 Omicron Variant AI-based Primers

As the COVID-19 pandemic continues to affect the world, a new variant of concern, B.1.1.529 (Omicron), has been recently identified by the World Health Organization. At the time of writing, there are still no available primer sets specific to the Omicron variant, and its identification is only possible by using multiple targets, checking for specific failures, amplifying the suspect samples, and sequencing the results. This procedure is considerably time-consuming, in a situation where time might be of the essence. In this paper we use an Artificial Intelligence (AI) technique to identify a candidate primer set for the Omicron variant. The technique, based on Evolutionary Algorithms (EAs), has been already exploited in the recent past to develop primers for the B.1.1.7/Alpha variant, that have later been successfully tested in the lab. Starting from available virus samples, the technique explores the space of all possible subsequences of viral RNA, evaluating them as candidate primers. The criteria used to establish the suitability of a sequence as primer includes its frequency of appearance in samples labeled as Omicron, its absence from samples labeled as other variants, a specific range of melting temperature, and its CG content. The resulting primer set has been validated in silico and proves successful in preliminary laboratory tests. Thus, these results prove further that our technique could be established as a working template for a quick response to the appearance of new SARS-CoV-2 variants.

bioinformatics↗

bioRxiv2021

Design of Specific Primer Sets for the Detection of B.1.1.7, B.1.351 and P.1 SARS-CoV-2 Variants using Deep Learning

As the COVID-19 pandemic continues, new SARS-CoV-2 variants with potentially dangerous features have been identified by the scientific community. Variant B.1.1.7 lineage clade GR from Global Initiative on Sharing All Influenza Data (GISAID) was first detected in the UK, and it appears to possess an increased transmissibility. At the same time, South African authorities reported variant B.1.351, that shares several mutations with B.1.1.7, and might also present high transmissibility. Earlier this year, a variant labelled P.1 with 17 non-synonymous mutations was detected in Brazil. Recently the World Health Organization has raised concern for the variants B.1.617.2 mainly detected in India but now exported worldwide. It is paramount to rapidly develop specific molecular tests to uniquely identify new variants. Using a completely automated pipeline built around deep learning and evolutionary algorithms techniques, we designed primer sets specific to variants B.1.1.7, B.1.351, P.1 and respectively. Starting from sequences openly available in the GISAID repository, our pipeline was able to deliver the primer sets for each variant. In-silico tests show that the sequences in the primer sets present high accuracy and are based on 2 mutations or more. In addition, we present an analysis of key mutations for SARS-CoV-2 variants. Finally, we tested the designed primers for B.1.1.7 using RT-PCR. The presented methodology can be exploited to swiftly obtain primer sets for each new variant, that can later be a part of a multiplexed approach for the initial diagnosis of COVID-19 patients.

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bioRxiv2020

Design of Specific Primer Set for Detection of B.1.1.7 SARS-CoV-2 Variant using Deep Learning

The SARS-CoV-2 variant B.1.1.7 lineage, also known as clade GR from Global Initiative on Sharing All Influenza Data (GISAID), Nextstrain clade 20B, or Variant Under Investigation in December 2020 (VUI - 202012/01), appears to have an increased transmissability in comparison to other variants. Thus, to contain and study this variant of the SARS-CoV-2 virus, it is necessary to develop a specific molecular test to uniquely identify it. Using a completely automated pipeline involving deep learning techniques, we designed a primer set which is specific to SARS-CoV-2 variant B.1.1.7 with >99% accuracy, starting from 8,923 sequences from GISAID. The resulting primer set is in the region of the synonymous mutation C16176T in the ORF1ab gene, using the canonical sequence of the variant B.1.1.7 as a reference. Further in-silico testing shows that the primer sets sequences do not appear in different viruses, using 20,571 virus samples from the National Center for Biotechnology Information (NCBI), nor in other coronaviruses, using 487 samples from National Genomics Data Center (NGDC). In conclusion, the presented primer set can be exploited as part of a multiplexed approach in the initial diagnosis of Covid-19 patients, or used as a second step of diagnosis in cases already positive to Covid-19, to identify individuals carrying the B.1.1.7 variant.

bioinformatics↗

bioRxiv2020

Accurate Identification of SARS-CoV-2 from Viral Genome Sequences using Deep Learning

In this paper, deep learning is coupled with explainable artificial intelligence techniques for the discovery of representative genomic sequences in SARS-CoV-2. A convolutional neural network classifier is first trained on 553 sequences from available repositories, separating the genome of different virus strains from the Coronavirus family with considerable accuracy. The networks behavior is then analyzed, to discover sequences used by the model to identify SARS-CoV-2, ultimately uncovering sequences exclusive to it. The discovered sequences are first validated on samples from other repositories, and proven able to separate SARS-CoV-2 from different virus strains with near-perfect accuracy. Next, one of the sequences is selected to generate a primer set, and tested against other state-of-the-art primer sets on existing datasets, obtaining competitive results. Finally, the primer is synthesized and tested on patient samples (n=6 previously tested positive), delivering a sensibility similar to routine diagnostic methods, and 100% specificity. In this paper, deep learning is coupled with explainable artificial intelligence techniques for the discovery of representative genomic sequences in SARS-CoV-2. A convolutional neural network classifier is first trained on 553 sequences from NGDC, separating the genome of different virus strains from the Coronavirus family with accuracy 98.73%. The networks behavior is then analyzed, to discover sequences used by the model to identify SARS-CoV-2, ultimately uncovering sequences exclusive to it. The discovered sequences are validated on samples from NCBI and GISAID, and proven able to separate SARS-CoV-2 from different virus strains with near-perfect accuracy. Next, one of the sequences is selected to generate a primer set, and tested against other state-of-the-art primer sets, obtaining competitive results. Finally, the primer is synthesized and tested on patient samples (n=6 previously tested positive), delivering a sensibility similar to routine diagnostic methods, and 100% specificity. The proposed methodology has a substantial added value over existing methods, as it is able to both identify promising primer sets for a virus from a limited amount of data, and deliver effective results in a minimal amount of time. Considering the possibility of future pandemics, these characteristics are invaluable to promptly create specific detection methods for diagnostics.

bioinformatics↗

bioRxiv2018

Ensemble Feature Selection and Meta-Analysis of Cancer miRNA Biomarkers

The role of microRNAs (miRNAs) in cellular processes captured the attention of many researchers, since their dysregulation is shown to affect the cancer disease landscape by sustaining proliferative signaling, evading program cell death, and inhibiting growth suppressors. Thus, miRNAs have been considered important diagnostic and prognostic biomarkers for several types of tumors. Machine learning algorithms have proven to be able to exploit the information contained in thousands of miRNAs to accurately predict and classify cancer types. Nevertheless, extracting the most relevant miRNA expressions is fundamental to allow human experts to validate and make sense of the results obtained by automatic algorithms. We propose a novel feature selection approach, able to identify the most important miRNAs for tumor classification, based on consensus on feature relevance from high-accuracy classifiers of different typologies. The proposed methodology is tested on a real-world dataset featuring 8,129 patients, 29 different types of tumors, and 1,046 miRNAs per patient, taken from The Cancer Genome Atlas (TCGA) database. A new miRNA signature is suggested, containing the 100 most important oncogenic miRNAs identified by the presented approach. Such a signature is proved to be sufficient to identify all 29 types of cancer considered in the study, with results nearly identical to those obtained using all 1,046 features in the original dataset. Subsequently, a meta-analysis of the medical literature is performed to find references to the most important biomarkers extracted by the methodology. Besides known oncomarkers, 15 new miRNAs previously not ranked as important biomarkers for diagnosis and prognosis in cancer pathologies are uncovered. Such miRNAs, considered relevant by the machine learning algorithms, but still relatively unexplored by specialized literature, could provide further insights in the biology of cancer.

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