T2T-YAO: A Telomere-to-telomere Assembled Diploid Reference Genome for Han Chinese

Since its initial release in 2001,the human reference genome has undergone continuous improvement in quality,and the recently released telomere-to-telomere(T2T)version-T2T-CHM13—reaches its highest level of continuity and accuracy after 20 years of effort by working on a simplified,nearly homozygous genome of a hydatidiform mole cell line.Here,to provide an authentic complete diploid human genome reference for the Han Chinese,the largest population in the world,we assembled the genome of a male Han Chinese individual,T2T-YAO,which includes T2T assemblies of all the 22+X+M and 22+Y chromosomes in both haploids.The quality of T2T-YAO is much better than those of all currently available diploid assemblies,and its haploid version,T2T-YAO-hp,generated by selecting the better assembly for each autosome,reaches the top quality of fewer than one error per 29.5 Mb,even higher than that of T2T-CHM13.Derived from an individual living in the aboriginal region of the Han population,T2T-YAO shows clear ancestry and potential genetic continuity from the ancient ancestors.Each haplotype of T2TYAO possesses330-Mb exclusive sequences,3100 unique genes,and tens of thousands of nucleotide and structural variations as compared with CHM13,highlighting the necessity of a population-stratified reference genome.The construction of T2T-YAO,an accurate and authentic representative of the Chinese population,would enable precise delineation of genomic variations and advance our understandings in the hereditability of diseases and phenotypes,especially within the context of the unique variations of the Chinese population.

Comprehensive Humoral and Cellular Immune Responses to SARS-CoV-2 Variants in Diverse Chinese Population

The SARS-CoV-2 variants have been emerging and have made great challenges to current vaccine and pandemic control strategies.It is urgent to understand the current immune status of various Chinese populations given that the preexisting immunity has been established by national vaccination or ex posure to past variants.Using sera from 85 individuals(including 21 convalescents of natural infection,15 cases which suffered a breakthrough infection after being fully vaccinated,and 49 healthy vaccinees),we showed signifcantly enhanced neutralizing activities against SRAS-CoV-2 variants in convalescent sera,especially those who had been fully vaccinated.The neut ralizing antibodies against Omicron were detectable in 75%of convalescents and 4.9%of healthy vaccinees(p=0.006),with a GMT of 289.5,180.9-463.3,and 42.6,31.3-59,respetively.However,the neutralizing activities were weaker in young convalescents(aged<18y),with a detectable rate of 50%and a GMT of 46.4 against Omicron.We also examined and found no pan.sarbecovirus neutralizing activities in vaccinated SARS-CoV-I survivors.A booster dose could further increase the breadth and magnitude of neutralization against WT and variants of concern(VOCs)to different degrees.In addition,we showed that COVID-19-inactivated vaccines can elicit Omicron-specific T-cell responses.The positive rates of ELISpot reactions were 26.7%(4/15)and 43.8%(7/16)in the full vaccination group and the booster vaccination group,respectively,although without statistically significant difference.The neutralizing antibody titers declined while T-cell responses remain consistent over 6 months.These findings will inform the optimization of public health vaccination and intervention strategies to protect diverse populations against SARS-CoV-2 variants.Advances.Breakthrough infection significantly boosted neutralizing activities against SARS-CoV-2 variants a compared to booster immunization with inaclivated vaccine.Vaccine-induced vir us-specific T-cell immunity,on the other hand,may compensate for the shortall.Furthermore,the public health system should target the most vulnerable group due to a poorer protective serological response in both infected and vaccinated adolescents.