Stewart Cole | EPFL Graph Search

Professor Stewart Cole is an international authority in bacterial molecular-genetics and genomics. He has made outstanding contributions in several fields including: bacterial anaerobic electron transport; genome analysis of retroviruses and papillomaviruses; antibiotic resistance mechanisms; and the molecular microbiology of toxigenic clostridia. His studies on isoniazid and multidrug resistance in Mycobacterium tuberculosis, together with his pioneering work on the pathogenicity, evolution and genomics of the tubercle and leprosy bacilli, have made him an undisputed leader in the field of mycobacterial research. The findings of his research are of direct relevance to public health and disease-control in both the developing world and the industrialised nations. He has published over 250 scientific papers and review articles, and holds many patents.

The DESI Survey Validation: Results from Visual Inspection of Bright Galaxies, Luminous Red Galaxies, and Emission-line Galaxies

Stewart Cole, Arjun Dey, Anand Stéphane Raichoor, Yi Zhang

The Dark Energy Spectroscopic Instrument (DESI) Survey has obtained a set of spectroscopic measurements of galaxies to validate the final survey design and target selections. To assist in these tasks, we visually inspect DESI spectra of approximately 2500 bright galaxies, 3500 luminous red galaxies (LRGs), and 10,000 emission-line galaxies (ELGs) to obtain robust redshift identifications. We then utilize the visually inspected redshift information to characterize the performance of the DESI operation. Based on the visual inspection (VI) catalogs, our results show that the final survey design yields samples of bright galaxies, LRGs, and ELGs with purity greater than 99%. Moreover, we demonstrate that the precision of the redshift measurements is approximately 10 km s(-1) for bright galaxies and ELGs and approximately 40 km s(-1) for LRGs. The average redshift accuracy is within 10 km s(-1) for the three types of galaxies. The VI process also helps improve the quality of the DESI data by identifying spurious spectral features introduced by the pipeline. Finally, we show examples of unexpected real astronomical objects, such as Ly alpha emitters and strong lensing candidates, identified by VI. These results demonstrate the importance and utility of visually inspecting data from incoming and upcoming surveys, especially during their early operation phases.

IOP Publishing Ltd2023

Development and validation of a multiplex real-time qPCR assay using GMP-grade reagents for leprosy diagnosis

Charlotte Avanzi, Stewart Cole, Thyago Leal Calvo

Author summaryLeprosy is a chronic dermato-neurological disease caused by Mycobacterium leprae, an obligate intracellular bacterium. Diagnosis of leprosy often relies on skin examinations for clinical signs, bacilli staining from skin smears and invasive skin biopsies. However, the spectrum of clinical manifestations and, often, low bacilli numbers can hinder accurate diagnosis. Timely detection is a challenge in leprosy diagnosis, relying on clinical examination and requiring trained health professionals. Proper intervention for adequate care and transmission control depends on early and reliable pathogen detection. Quantitative PCR methods for detecting bacterial DNA are more sensitive and could aid in differentially diagnosing leprosy from other dermatological conditions. In this work, we present a new multiplex PCR that was assessed for quality control standards, and the data indicate that the assay is stable and reproducible. The results presented here are the basis of a novel and robust tool with potential to increase the accuracy of leprosy diagnosis in routine or reference laboratories. Leprosy is a chronic dermato-neurological disease caused by Mycobacterium leprae, an obligate intracellular bacterium. Timely detection is a challenge in leprosy diagnosis, relying on clinical examination and trained health professionals. Furthermore, adequate care and transmission control depend on early and reliable pathogen detection. Here, we describe a qPCR test for routine diagnosis of leprosy-suspected patients. The reaction simultaneously amplifies two specific Mycobacterium leprae targets (16S rRNA and RLEP), and the human 18S rRNA gene as internal control. The limit of detection was estimated to be 2.29 copies of the M. leprae genome. Analytical specificity was evaluated using a panel of 20 other skin pathogenic microorganisms and Mycobacteria, showing no cross-reactivity. Intra- and inter-operator C-p variation was evaluated using dilution curves of M. leprae DNA or a synthetic gene, and no significant difference was observed between three operators in two different laboratories. The multiplex assay was evaluated using 97 patient samples with clinical and histopathological leprosy confirmation, displaying high diagnostic sensitivity (91%) and specificity (100%). Validation tests in an independent panel of 50 samples confirmed sensitivity and specificity of 97% and 98%, respectively. Importantly, assay performance remained stable for at least five months. Our results show that the newly developed multiplex qPCR effectively and specifically detects M. leprae DNA in skin samples, contributing to an efficient diagnosis that expedites the appropriate treatment.

PUBLIC LIBRARY SCIENCE2022

Gene expression patterns associated with multidrug therapy in multibacillary leprosy

Charlotte Avanzi, Andrej Benjak, Philippe Busso, Stewart Cole, Thyago Leal Calvo

Multidrug therapy (MDT) has been successfully used in the treatment of leprosy. However, although patients are cured after the completion of MDT, leprosy reactions, permanent disability, and occasional relapse/reinfection are frequently observed in patients. The immune system of multibacillary patients (MB) is not able to mount an effective cellular immune response against M. leprae. Consequently, clearance of bacilli from the body is a slow process and after 12 doses of MDT not all MB patients reduce bacillary index (BI). In this context, we recruited MB patients at the uptake and after 12-month of MDT. Patients were stratified according to the level of reduction of the BI after 12 doses MDT. A reduction of at least one log in BI was necessary to be considered a responder patient. We evaluated the pattern of host gene expression in skin samples with RNA sequencing before and after MDT and between samples from patients with or without one log reduction in BI. Our results demonstrated that after 12 doses of MDT there was a reduction in genes associated with lipid metabolism, inflammatory response, and cellular immune response among responders (APOBEC3A, LGALS17A, CXCL13, CXCL9, CALHM6, and IFNG). Also, by comparing MB patients with lower BI reduction versus responder patients, we identified high expression of CDH19, TMPRSS4, PAX3, FA2H, HLA-V, FABP7, and SERPINA11 before MDT. From the most differentially expressed genes, we observed that MDT modulates pathways related to immune response and lipid metabolism in skin cells from MB patients after MDT, with higher expression of genes like CYP11A1, that are associated with cholesterol metabolism in the group with the worst response to treatment. Altogether, the data presented contribute to elucidate gene signatures and identify differentially expressed genes associated with MDT outcomes in MB patients.

FRONTIERS MEDIA SA2022