105P RADseq for tumour mutation burden estimation and mutation signature analysis

نویسندگان

چکیده

Tumour mutation burden (TMB) is a biomarker for cancer immune checkpoint blockade (ICB) response, and signatures provide “life history” of tumour evolution. Researchers have repurposed gene panels (CGPs) to cheaply estimate these parameters. The low coverage CGPs, however, may be problematic in the exploration TMB as ICB. Restriction enzyme associated DNA sequencing (RADseq) uses restriction enzymes achieve at random loci throughout genome. It was hypothesised that RADseq could recapitulate breast samples. In silico libraries were generated by scanning human genome cut sites filtering regions with adjacent sites. resulting fragments overlapped mutations from whole (WGS) genomes. evaluated terms accuracy estimation profile recapitulation, compared CGP used A mouse cell line transfected APOBEC enzymes, which are known cause cancer, profiled using RADseq. Using cosine similarity (CS) WGS measure recapitulation quality, able signatures, while performed relatively poorly this regard (e.g. enzyme_1 CS=0.90±0.06 vs CS=0.28±0.19). had higher error than an library comparable (CGP range 0.0034-8.83 mutations/mb enzyme_2 0.0029-7.50, Wilcox p<0.001). RADseq, increased signature detected APOBEC3A, both absent control lines. methods do not accurately capture “genome-wide” parameters such signatures. This warrants investigation into whether can ICB trials. By comparison, offer cheap, effective solution estimation. also use researchers seeking study evolution model systems, we demonstrated.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

DNA Sequence Fragment Containing C to A Mutation as a Convenient Mutation Standard for DHPLC Analysis

Objective(s):  Denaturing high performance liquid chromatography (DHPLC) is a high throughput approach for screening DNA sequence variations. To assess oven calibration, cartridge performance, buffer composition and stability, the WAVE Low and High Range Mutation Standards are employed to ensure reproducibility and accuracy of the chromatographic analysis. The purpose of this study was to provi...

متن کامل

Mutation Analysis for Security

Security has become, nowadays, a major concern for the organizations as the majority of its applications are exposed to Internet, which increases the threats of security considerably. Thus, the solution is to improve tools and mechanisms to strengthen the protection of applications against attacks and ensure the different security objectives. Among solutions we will talking about, in this paper...

متن کامل

Mutation Coverage Estimation for Model Checking

When engineers design a system, there is always a question about how exhaustive the system has been examined to be correct. Coverage estimation provides an answer to this question in testing. A model checker verifies a design exhaustively, and proves the satisfaction of property specifications. However, people have noticed that design errors exist even after model checking is done, which goes t...

متن کامل

dna sequence fragment containing c to a mutation as a convenient mutation standard for dhplc analysis

objective(s):  denaturing high performance liquid chromatography (dhplc) is a high throughput approach for screening dna sequence variations. to assess oven calibration, cartridge performance, buffer composition and stability, the wave low and high range mutation standards are employed to ensure reproducibility and accuracy of the chromatographic analysis. the purpose of this study was to provi...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

ژورنال

عنوان ژورنال: Annals of Oncology

سال: 2022

ISSN: ['0923-7534', '1569-8041']

DOI: https://doi.org/10.1016/j.annonc.2022.09.106