A comparative genomics analysis of lung adenocarcinoma for Chinese population by using panel of recurrent mutations

Previous studies have demonstrated that Chinese lung adenocarcinoma(LUAD)patients have unique genetic characteristics,however,the specific genomic features relating to the development and treatment of LUAD in the Chinese population are not fully understood.Here,we applied the ultra-deep targeted sequencing to 66 Chinese LUAD samples,accompanied by comparative analysis with 162 Caucasian LUAD in The Cancer Genome Atlas.We focused on the 68 recurrently mutated genes and results revealed that the panel-based tumor mutational burden(pTMB)is significantly higher in the Chinese LUAD(P=0.0017).Additionally,the percentage of smoking-associated C>A transversion is significantly lower in Chinese LUAD(15.5%vs.39.7%,P=5.69×10^(-27)),while C>T transition is more frequent in Chinese LUAD(35.8%vs.25.7%,P=2.67×10^(-5)),which indicated the ethnic difference in mutation types.Notably,novel driver genes(GNAS and JAK1)that are peculiar to Chinese LUAD were identified,and a more convergent distribution of mutations was observed in the Chinese cohort(P=0.012)compared with scattered mutations in Caucasian LUAD.Our results present a distinct genomic profile of Chinese LUAD compared to Caucasians LUAD and elucidate the ethnic difference in mutation distribution besides the type and rate.

The genomic characteristics and pathogenicity of a mammalian orthoreovirus within a new lineage from wild pika in plateau

Emerging and re-emerging viruses from wild animals have seriously threatened the health of humans and domesticated animals in recent years.Herein,we isolated a new mammalian orthoreovirus(MRV),Pika/MRV/GCCDC7/2019(PMRV-GCCDC7),in the Qinghai-Tibet Plateau wild pika(Ochotona curzoniae).Though the PMRVGCCDC7 shows features of a typical reovirus with ten gene segments arranged in 3:3:4 in length,the virus belongs to an independent evolutionary branch compared to other MRVs based on phylogenetic tree analysis.The results of cellular susceptibility,species tropism,and replication kinetics of PMRV-GCCDC7 indicated the virus could infect four human cell lines(A549,Huh7,HCT,and LoVo)and six non-human cell lines,including Vero-E6,LLCMK2,BHK-21,N2a,MDCK,and RfKT cell,derived from diverse mammals,i.e.monkey,mice,canine and bat,which revealed the potential of PMRV-GCCDC7 to infect a variety of hosts.Infection of BALB/c mice with PMRVGCCDC7 via intranasal inoculation led to relative weight loss,lung tissue damage and inflammation with the increase of virus titer,but no serious respiratory symptoms and death occurred.The characterization of the new reovirus from a plateau-based wild animal has expanded our knowledge of the host range of MRV and provided insight into its risk of trans-species transmission and zoonotic diseases.

Genomic Characteristics of SARS-CoV,MERS-CoV and 2019-nCoV

In December 2019, Wuhan, the capital of Hubei Province in China,reported a series of unexplained cases of pneumonia, which has been confirmed to be an acute infectious respiratory disease caused by Novel Corona Virus 2019(2019-nCoV)infection. The World Health Organization(WHO) named this pneumonia Corona Virus Disease 2019(COVID-19). The 21 st century had witnessed the spread of two previously unrecognized coronaviruses around the world with high pathogenicity before, namely severe acute respiratory syndrome coronavirus(SARS-CoV) and Middle East respiratory syndrome coronavirus(MERS-CoV) respectively. At present, 2019-nCoV ’s genome has been sequenced by researchers all over the world represented by China. Based on the systematic review and analysis of the genomic sequence characteristics of three highly pathogenic coronaviruses, this paper expounds the basic characteristics of the genomes of SARS-CoV, MERS-CoV and 2019-nCoV,which all belong to β-coronaviruses, the functionally important ORFs, ORF1 a, ORF1 b and major structural proteins including the spike(S), membrane(M) and envelop(E) and nucleiccapsid(N) proteins have no significant difference with each other. However, as the majority of genetic variations being seen at the N-terminal part of S protein, 2019-nCoV aligned best with the bat SARS-like virus bat-SL-CoVZX45. And Structure analysis of the spike(S) protein of2019-nCoV showed that it’s S protein only binds weakly to the Angiotensin Converting Enzyme2(ACE2) receptor on human cells whereas the human SARS-Cov exhibits high affinity to the ACE receptor and MERS-Cov does not need ACE2 to infect human cells,its receptor on human cells is DPP4. In the future, we hope to provide new ideas for the prevention and treatment of coronavirus by strengthening the research of coronavirus S protein and ACE2 receptor, and continuous surveillance and genomic characterization of coronaviruses from bats are necessary due to potential risks of human infection induced by a genetic mutation.

Importation of SARS-CoV-2 Omicron variant in Beijing,China

Omicron(B.1.1.529),the fifth variant of concern(VOC)of severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2),was firstly identified in November 2021 in South Africa.Omicron contains far more genome mutations than any other VOCs ever found,raising significant concerns about its increased transmissibility and immune evasion.Here,we report the importation of the Omicron variant into Beijing,China,in December 2021.Full‐length genome sequences of five imported strains were obtained,with their genetic features characterized.Each strain contained 57 to 61 nucleotide substitutions,39 deletions,and 9 insertions in the genome.Thirty to thirty‐two amino acid changes were found in the spike proteins of the five strains.The phylogenetic tree constructed by the maximum likelihood method showed that all five imported genomes belonged to Omicron(BA.1)(alias of B.1.1.529.1),which is leading to the current surge of coronavirus disease 2019(COVID‐19)cases worldwide.The globally increased COVID‐19 cases driven by the Omicron variant pose a significant challenge to disease prevention and control in China.Continuous viral genetic surveillance and increased testing among international travellers are required to contain this highly contagious variant.