The cynomolgus and Chinese rhesus macaques are used as animal models in biomedical research. Yan et al. sequence their genomes and compare the sequences to that of the Indian rhesus macaque, providing a genetic foundation for interpreting research results. The nonhuman primates most commonly used in medical research are from the genus Macaca1. To better understand the genetic differences between these animal models, we present high-quality draft genome sequences from two macaque species, the cynomolgus/crab-eating macaque and the Chinese rhesus macaque. Comparison with the previously sequenced Indian rhesus macaque reveals that all three macaques maintain abundant genetic heterogeneity, including millions of single-nucleotide substitutions and many insertions, deletions and gross chromosomal rearrangements. By assessing genetic regions with reduced variability, we identify genes in each macaque species that may have experienced positive selection. Genetic divergence patterns suggest that the cynomolgus macaque genome has been shaped by introgression after hybridization with the Chinese rhesus macaque. Macaque genes display a high degree of sequence similarity with human disease gene orthologs and drug targets. However, we identify several putatively dysfunctional genetic differences between the three macaque species, which may explain functional differences between them previously observed in clinical studies.

To further reveal the phylogenetic evolution and molecular characteristics of the whole genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on a large number of genomes and provide a basis for the prevention and treatment of SARS-CoV-2. Various evolution analysis methods were employed. The estimated ratio of the rates of non-synonymous to synonymous changes (Ka/Ks) of SARS-CoV-2 was 1.008 or 1.094 based on 622 or 3624 SARS-CoV-2 genomes and nine key specific sites of high linkage, and four major haplotypes were found: H1, H2, H3 and H4. The results of Ka/Ks, detected population size and development trends of each major haplotype showed that H3 and H4 subgroups were going through a purify evolution and almost disappeared after detection, indicating that they might have existed for a long time. The H1 and H2 subgroups were going through a near neutral or neutral evolution and globally increased with time, and the frequency of H1 was generally high in Europe and correlated with the death rate (r >0.37), suggesting that these two haplotypes might relate to the infectivity or pathogenicity of SARS-CoV-2. Several key specific sites and haplotypes related to the infectivity or pathogenicity of SARS-CoV-2, and the possible earlier origin time and place of SARS-CoV-2 were indicated based on the evolution and epidemiology of 16,373 SARS-CoV-2 genomes.

Non-human primates have emerged as an important resource for the study of human disease and evolution. The characterization of genomic variation between and within non-human primate species could advance the development of genetically defined non-human primate disease models. However, non-human primate specific reagents that would expedite such research, such as exon-capture tools, are lacking. We evaluated the efficiency of using a human exome capture design for the selective enrichment of exonic regions of non-human primates. We compared the exon sequence recovery in nine chimpanzees, two crab-eating macaques and eight Japanese macaques. Over 91% of the target regions were captured in the non-human primate samples, although the specificity of the capture decreased as evolutionary divergence from humans increased. Both intra-specific and inter-specific DNA variants were identified; Sanger-based resequencing validated 85.4% of 41 randomly selected SNPs. Among the short indels identified, a majority (54.6%–77.3%) of the variants resulted in a change of 3 base pairs, consistent with expectations for a selection against frame shift mutations. Taken together, these findings indicate that use of a human design exon-capture array can provide efficient enrichment of non-human primate gene regions. Accordingly, use of the human exon-capture methods provides an attractive, cost-effective approach for the comparative analysis of non-human primate genomes, including gene-based DNA variant discovery.

In this study, we present a new method for evaluating animal evolutionary relationships. We used the GC% levels of genome‐wide genes to determine the correlation between the GC% content and evolutionary relationship. The correlation coefficients of the GC% content of the orthologous genes of the paired animal species were calculated for a total of 21 species, and the evolutionary branching dates of these 21 species were derived from fossil records. The correlation coefficient of the GC% content of the orthologous genes of the species pair under study served as an indicator of their evolutionary relationship. Moreover, there was a decreasing linear relationship between the correlation coefficient and evolutionary branching date (R ² = 0.930).

Dynamic changes in ctDNA variant allele frequency reflect real-time therapeutic efficacy. Timely treatment modification guided by ctDNA variant allele frequency may enable precision selection of optimized regimens to counteract evolving resistance in breast cancer. In this study, we developed a therapeutic approach integrating ctDNA dynamics with sequential organoid drug screening to optimize breast cancer treatment. Targeted deep sequencing on plasma samples from 71 patients with breast cancer revealed that ctDNA clearance correlates with improved disease-free survival. Additionally, analysis of 40 breast cancer organoid models demonstrated the potential of organoid culture supernatants for comprehensive mutation profiling and drug sensitivity testing. Together, these findings suggest that combining ctDNA monitoring with organoid-based drug screening can guide adjustments to treatment strategies, offering a promising solution to optimize patient outcomes. Significance: Monitoring circulating tumor DNA in combination with drug screening of organoids enables dynamic, personalized breast cancer therapy adjustments to overcome resistance and improve treatment efficacy.

Chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) is a heterogeneous disease in Western and Chinese populations, and it is still not well characterized in Chinese patients. Based on a large cohort of newly diagnosed CLL/SLL patients from China, we investigated immunophenotypes, genetic abnormalities, and their correlations. Eighty-four percent of the CLL/SLL patients showed typical immunophenotypes with scores of 4 or 5 points in the Royal Marsden Hospital (RMH) scoring system (classic group), and the remaining 16% of patients were atypical with scores lower than 4 points (atypical group). Trisomy 12 and variants of TP53, NOTCH1, SF3B1, ATM, and MYD88 were the most recurrent genetic aberrations. Additionally, unsupervised genomic analysis based on molecular genetics revealed distinctive characteristics of MYD88 variants in CLL/SLL. By overlapping different correlation grouping analysis from genetics to immunophenotypes, the results showed MYD88 variants to be highly related to atypical CLL/SLL immunophenotypes. Furthermore, compared with mantle cell lymphoma (MCL), the genetic landscape showed potential value in clinical differential diagnosis of atypical CLL/SLL and MCL patients. These results reveal immunophenotypic and genetic features, and may provide insights into the tumorigenesis and clinical management of Chinese CLL/SLL patients.