J 2024

A computational workflow for analysis of missense mutations in precision oncology

KHAN, Rayyan Tariq; Petra POKORNÁ; Jan DVORSKÝ; Simeon BORKO; Ihor AREFIEV et. al.

Basic information

Original name

A computational workflow for analysis of missense mutations in precision oncology

Authors

KHAN, Rayyan Tariq (586 Pakistan, belonging to the institution); Petra POKORNÁ (203 Czech Republic, belonging to the institution); Jan DVORSKÝ (203 Czech Republic, belonging to the institution); Simeon BORKO (703 Slovakia, belonging to the institution); Ihor AREFIEV (804 Ukraine, belonging to the institution); Joan PLANAS IGLESIAS (724 Spain, belonging to the institution); Adam DOBIÁŠ (703 Slovakia, belonging to the institution); José Gaspar RANGEL PAMPLONA PIZARRO PINTO (620 Portugal, belonging to the institution); Veronika SZOTKOWSKÁ (203 Czech Republic, belonging to the institution); Jaroslav ŠTĚRBA (203 Czech Republic, belonging to the institution); Ondřej SLABÝ (203 Czech Republic, belonging to the institution); Jiří DAMBORSKÝ (203 Czech Republic, belonging to the institution); Stanislav MAZURENKO (643 Russian Federation, belonging to the institution) and David BEDNÁŘ (203 Czech Republic, guarantor, belonging to the institution)

Edition

JOURNAL OF CHEMINFORMATICS, ENGLAND, BMC, 2024, 1758-2946

Other information

Language

English

Type of outcome

Article in a journal

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

is not subject to a state or trade secret

References:

URL

RIV identification code

RIV/00216224:14310/24:00136618

Organization

Přírodovědecká fakulta – Repository – Repository

DOI

http://dx.doi.org/10.1186/s13321-024-00876-3

UT WoS

001281138800001

EID Scopus

2-s2.0-85199996054

Keywords in English

Bioinformatics; Cancer; Function; High-performance computing; Machine learning; Molecular modelling; Oncology; Personalised medicine; Single nucleotide polymorphism; Stability; Treatment

Links

FW03010208, research and development project. LM2018140, research and development project. LX22NPO5102, research and development project. MUNI/A/1625/2023, interní kód Repo. NU20-03-00240, research and development project. TN02000109, research and development project. 857560, interní kód Repo. CZECRIN IV, large research infrastructures. RECETOX RI II, large research infrastructures.
Changed: 24/6/2025 00:50, RNDr. Daniel Jakubík

Abstract

V originále

Every year, more than 19 million cancer cases are diagnosed, and this number continues to increase annually. Since standard treatment options have varying success rates for different types of cancer, understanding the biology of an individual's tumour becomes crucial, especially for cases that are difficult to treat. Personalised high-throughput profiling, using next-generation sequencing, allows for a comprehensive examination of biopsy specimens. Furthermore, the widespread use of this technology has generated a wealth of information on cancer-specific gene alterations. However, there exists a significant gap between identified alterations and their proven impact on protein function. Here, we present a bioinformatics pipeline that enables fast analysis of a missense mutation’s effect on stability and function in known oncogenic proteins. This pipeline is coupled with a predictor that summarises the outputs of different tools used throughout the pipeline, providing a single probability score, achieving a balanced accuracy above 86%. The pipeline incorporates a virtual screening method to suggest potential FDA/EMA-approved drugs to be considered for treatment. We showcase three case studies to demonstrate the timely utility of this pipeline. To facilitate access and analysis of cancer-related mutations, we have packaged the pipeline as a web server, which is freely available at https://loschmidt.chemi.muni.cz/predictonco/.
Displayed: 8/8/2025 08:31