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LATVIAN

BIOMEDICAL

RESEARCH AND STUDY CENTRE


RESEARCH AND EDUCATION IN BIOMEDICINE FROM GENES TO HUMAN

Project Title: „Whole genome sequencing of tuberculosis for routine clinical use in Latvia: evidence-based design and concept evaluation.”

Funding: European Regional Development Fund (ERDF), Measure 1.1.1.1 “Support for applied research”

Project No.: 1.1.1.1/20/A/046

Period: 1 January 2021 – 30 November 2023

Project costs: 540 540.54 EUR

Principle Investigator: Dr. biol. Renāte Ranka

Cooperation partner: SIA “GenEra”

Project summary:

The aim of this project is to design and evaluate an approach of introducing the whole genome sequencing of M. tuberculosis into routine clinical practice in Latvia.

Tuberculosis remains one of the most devastating diseases affecting people of all ages across the globe. It is among the top 10 causes of death worldwide and has high economic impacts. The widespread transmission and prevalence of drug resistant variants of mycobacteria is one of the major obstacles for successful control of the disease. Patients infected with drug resistant strains are hard or even impossible to be cured, and their treatment is more toxic and expensive. In Latvia, multi-drug resistant tuberculosis remains a serious health problem: in 2017, almost 8% of all TB cases in Latvia were caused by drug-resistant M. tuberculosis strains.

Slow and cumbersome laboratory diagnostics for M. tuberculosis complex risk delayed treatment and poor patient outcomes. Whole-genome sequencing (WGS) could potentially provide a rapid and comprehensive diagnostic solution and is moving from proof-of-concept research into for routine clinical use.

 Information published 04.01.2021.

Progress of the project

1 January 2021 – 31 March 2021

The systematization of available DNA samples of M. tuberculosis isolates collected in previous studies was performed, which included checking the availability of phenotypic data and assessing the amount / purity of DNA. The first sample set, which included multidrug-resistant M. tuberculosis strains, was selected. Additional DNA purification was performed on samples with low DNA quality. Development of M. tuberculosis enrichment protocols has begun. Evaluation of available M. tuberculosis resistance mutation databases has been performed.

Information published 31.03.2021.

Progress of the project

1 April 2021 – 30 June 2021

Whole genome sequencing and data analysis was performed for the particular DNA sample set of M. tuberculosis isolates collected during the previous studies. The development of M. tuberculosis enrichment protocols has been continued. Evaluation of available M. tuberculosis resistance mutation databases has been continued. The conference thesis was presented and published at the 41st Annual Congress of the European Society of Mycobacteriology: Sadovska et al.,“WGS-based recurrent tuberculosis cause determination for patients involved in local outbreaks in Latvia”.

Information published 30.06.2021.

Progress of the project

1 July 2021 – 30 September 2021

We continued the whole genome sequencing and data analysis for the particular DNA sample sets of M. tuberculosis isolates collected during the previous studies. We performed the adaptation and improvement of several bioinformatics pipelines. The development of M. tuberculosis enrichment protocols has been continued. Evaluation of the detected M. tuberculosis resistance mutations in conjunction with phenotypic data has been started.

Information published 30.09.2021.

Progress of the project

1 October  2021 – 31 December 2021

Full genome sequencing and data analysis of DNA samples from several M. tuberculosis isolate collections has been continued during the reporting period. Significant differences in the quantity and quality of DNA have been identified due to the use of different DNA isolation methods for M. tuberculosis isolates from solid and liquid media. As a result, the adaptation of DNA purification and concentration protocols to the needs of the WGS has begun.

Information published 30.12.2021.

Progress of the project

1 January 2022 – 31 March 2022

Full genome sequencing and data analysis of several M. tuberculosis isolate sample sets collected in previous studies was continued. M. tuberculosis DNA samples obtained in a hospital laboratory using various DNA extraction methods have been evaluated and compared. Due to the very low concentration of M. tuberculosis DNA in some samples, which makes the use of NGS / WGS technologies very difficult, the workflows have been further adapted and refined. The aim, tasks and progress of the project were reported at the meeting of the Latvian Association of Tuberculosis and Lung Diseases Physicians (March 23, 2022).

Information published 31.03.2022.

Progress of the project

1 April 2022 – 30 June 2022

Summarising of the full genome sequencing data of several M. tuberculosis DNA sample sets has been carried out during the reporting period. An evaluation and in-depth analysis of the current sequencing results has been performed. Special attention was paid to the evaluation of the significance of the applied bioinformatics methods and data for the identification of M. tuberculosis resistance, as well as the tracking of epidemiological links. The work on the preparation of the scientific publication has been started. A student research thesis was defended in connection with the project topic.

Information published 30.06.2022.