Genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the only approach to rapidly monitor and tackle emerging variants of concern (VOC) of the COVID-19 pandemic. Such scrutiny is crucial to limit the spread of VOC that might escape the immune protection conferred by vaccination strategies. It is also becoming clear now that efficient genomic surveillance would require monitoring the host gene expression to identify prognostic biomarkers of efficacy and disease progression. Here we applied an integrated workflow for RNA extracted from nasal swabs to obtain in parallel the entire genome of SARS-CoV-2 and host respiratory epithelium transcriptome, representing the majority of Italian processed genomic samples. In addition, we have matured and applied novel proof-of-principle approaches to prioritize possible gain-of-function mutations by leveraging patients' metadata and isolated patient-specific signatures of SARS-CoV-2 infection. The goals mentioned above have all been achieved in a cost-effective manner that does not require automation, in an effort to allow any lab with a benchtop sequencer and a limited budget to perform integrated genomic surveillance on premises.

AN IMPROVED GENOMIC SURVEILLANCE APPROACH TO DISSECT THE SARS-COV-2 PANDEMIC / A. Grimaldi ; tutor: D. Cacchiarelli ; internal advisor: D. Di Bernardo ; external Advisor: N. Elvassore. Università degli Studi di Milano, 2022. 34. ciclo, Anno Accademico 2022.

AN IMPROVED GENOMIC SURVEILLANCE APPROACH TO DISSECT THE SARS-COV-2 PANDEMIC

A. Grimaldi
2022

Abstract

Genomic surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the only approach to rapidly monitor and tackle emerging variants of concern (VOC) of the COVID-19 pandemic. Such scrutiny is crucial to limit the spread of VOC that might escape the immune protection conferred by vaccination strategies. It is also becoming clear now that efficient genomic surveillance would require monitoring the host gene expression to identify prognostic biomarkers of efficacy and disease progression. Here we applied an integrated workflow for RNA extracted from nasal swabs to obtain in parallel the entire genome of SARS-CoV-2 and host respiratory epithelium transcriptome, representing the majority of Italian processed genomic samples. In addition, we have matured and applied novel proof-of-principle approaches to prioritize possible gain-of-function mutations by leveraging patients' metadata and isolated patient-specific signatures of SARS-CoV-2 infection. The goals mentioned above have all been achieved in a cost-effective manner that does not require automation, in an effort to allow any lab with a benchtop sequencer and a limited budget to perform integrated genomic surveillance on premises.
2022
tutor: D. Cacchiarelli ; internal advisor: D. Di Bernardo ; external Advisor: N. Elvassore
Dipartimento di Oncologia ed Emato-Oncologia
English
34
2022
MEDICINA DEI SISTEMI
Settore BIO/11 - Biologia Molecolare
Pubblicazione scientifica
RNAseq; Genomic surveillance; COVID-19; SARS-CoV-2; Whole Genome Sequencing; Integrative genomics
CACCHIARELLI DAVIDE,
Doctoral Thesis
Prodotti della ricerca::Tesi di dottorato
-2.0
open
Università degli Studi di Milano
info:eu-repo/semantics/doctoralThesis
1
A. Grimaldi
AN IMPROVED GENOMIC SURVEILLANCE APPROACH TO DISSECT THE SARS-COV-2 PANDEMIC / A. Grimaldi ; tutor: D. Cacchiarelli ; internal advisor: D. Di Bernardo ; external Advisor: N. Elvassore. Università degli Studi di Milano, 2022. 34. ciclo, Anno Accademico 2022.
File in questo prodotto:
File Dimensione Formato  
phd_unimi_R12419.pdf

accesso aperto

Descrizione: Tesi Dottorato
Tipologia: Altro
Dimensione 7.02 MB
Formato Adobe PDF
7.02 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/946458
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact