Massive‐scale genomic analysis reveals SARS‐CoV‐2 mutation characteristics and evolutionary trends

The severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)pandemic resulted in significant societal costs.Hence,an in‐depth understanding of SARS‐CoV‐2 virus mutation and its evolution will help determine the direction of the COVID‐19 pandemic.In this study,we identified 296,728 de novo mutations in more than 2,800,000 high‐quality SARS‐CoV‐2 genomes.All possible factors affecting the mutation frequency of SARS‐CoV‐2 in human hosts were analyzed,including zinc finger antiviral proteins,sequence context,amino acid change,and translation efficiency.As a result,we proposed that when adenine(A)and tyrosine(T)bases are in the context of AM(M stands for adenine or cytosine)or TA motif,A or T base has lower mutation frequency.Furthermore,we hypothesized that translation efficiency can affect the mutation frequency of the third position of the codon by the selection,which explains why SARS‐CoV‐2 prefers AT3 codons usage.In addition,we found a host‐specific asymmetric dinucleotide mutation frequency in the SARS‐CoV‐2 genome,which provides a new basis for determining the origin of the SARS‐CoV‐2.Finally,we summarize all possible factors affecting mutation frequency and provide insights into the mutation characteristics and evolutionary trends of SARS‐CoV‐2.

Correlation between BRAF^(V600E) mutation and clinicopathological features in pediatric papillary thyroid carcinoma

In adults, the presence of the BRAF^(V600E) mutation in papillary thyroid cancer(PTC) has been demonstrated to be strongly associated with aggressive cancer-cell characteristics and poor patient prognosis. In contrast, the frequency of this mutation in pediatric PTC has undergone limited study, and the few available estimates range from 0 to 63%. Furthermore, the role of the BRAF^(V600E) mutation in pediatric PTC is controversial; thus, the present study aimed to investigate the prevalence and role of the BRAF^(V600E) mutation in48 pediatric patients with PTC, aged 3–13 years. Of these patients, 41 were diagnosed with classic PTC, five were found to have a follicular variant of PTC, and two to exhibit a diffuse sclerosing PTC variant. The BRAF^(V600E) mutation was identified to be present in 35.4% of the 48 analyzed patients, and in 41.5% of the patients diagnosed with classical PTC. Furthermore, the presence of the BRAF^(V600E) mutation was found to be associated with a patient age at diagnosis of less than ten years(P=0.011), the performance of a thyroidectomy(P=0.03), exhibited tumor multifocality(P=0.02) and/or extra-thyroidal invasion(P=0.003), and both a low MACIS(Metastases, Age, Completeness of resection, Invasion, Size)(P=0.036) and AMES(Age, Metastasis, Extent of tumor,Size)(P=0.001)score. Together, these data suggest that the presence of the BRAF^(V600E) mutation may be negatively correlated with partial aggressive clinicopathological features of pediatric PTC.