While immune checkpoint inhibitors(ICIs)are adopted as standard therapy for advanced non-small cell lung cancer(NSCLC),genetic determinants of response heterogeneity remain elusive[1].As most hematopoietic lineages un...While immune checkpoint inhibitors(ICIs)are adopted as standard therapy for advanced non-small cell lung cancer(NSCLC),genetic determinants of response heterogeneity remain elusive[1].As most hematopoietic lineages undergo dynamic changes during tumor pathogenesis and immunotherapy[2],elucidating how germline variants modulate their transcriptomes is critical.Expression quantitative trait loci(eQTL)analysis,especially integrated with single-cell RNA sequencing(scRNA-seq),enables gene regulation mapping at single-cell resolution[3,4].Detailed methodologies are described in the Supplementary Materials.展开更多
Background： The dilemma of pathogens identification in patients with unidentified clinical symptoms such as lever of unknown origin exists, which not only poses a challenge to both the diagnostic and therapeutic proc...Background： The dilemma of pathogens identification in patients with unidentified clinical symptoms such as lever of unknown origin exists, which not only poses a challenge to both the diagnostic and therapeutic process by itself, but also to expert physicians. Methods： In this report, we have attempted to increase the awareness of unidentified pathogens by developing a method to investigate hitherto unidentified infectious pathogens based on unbiased high-throughput sequencing. Results： Our observations show that this method supplements current diagnostic technology that predominantly relies on information derived five cases from the intensive care unit. This methodological approach detects viruses and corrects the incidence of false positive detection rates of pathogens in a much shorter period. Through our method is followed by polymerase chain reaction validation, we could identify infection with Epstein-Barr virus, and in another case, we could identify infection with Streptococcus viridians based on the culture, which was false positive. Conclusions： This technology is a promising approach to revolutionize rapid diagnosis of infectious pathogens and to guide therapy that might result in the improvement of personalized medicine.展开更多
Background： Congenital cataract （CC） is the leading cause of visual impairment or blindness in children worldwide. Because of highly genetic and clinical heterogeneity, a molecular diagnosis of the lens disease rem...Background： Congenital cataract （CC） is the leading cause of visual impairment or blindness in children worldwide. Because of highly genetic and clinical heterogeneity, a molecular diagnosis of the lens disease remains a challenge. Methods： In this study, we tested a three-generation Chinese family with autosomal dominant CCs by targeted sequencing of 45 CC genes on next generation sequencing and evaluated the pathogenicity of the detected mutation by protein structure, pedigree validation, and molecular dynamics （MD） simulation. Results： A novel 15 bp deletion on GJA8 （c.426_440delGCTGGAGGGGACCCT or p. 143147delLEGTL） was detected in the family. The deletion, concerned with an in-frame deletion of 5 amino acid residues in a highly evolutionarily conserved region within the cytoplasmic loop domain of the gap junction channel protein connexin 50 （CxS0）, was in full cosegregation with the cataract phenotypes in the family but not found in 1100 control exomes. MD simulation revealed that the introduction of the deletion destabilized the Cx50 gap junction channel, indicating the deletion as a dominant-negative mutation, Conclusions： The above results support the pathogenic role of the 15 bp deletion on GJA8 in the Chinese family and demonstrate targeted genes sequencing as a resolution to molecular diagnosis of CCs.展开更多
To the Editor: Ellis van Creveld (EvC) syndrome is a rare, autosomal recessive skeletal dysplasia with the prevalence of 1/60,000 approximatelyJu It is characterized by short limbs, short ribs, postaxial polydactyly, ...To the Editor: Ellis van Creveld (EvC) syndrome is a rare, autosomal recessive skeletal dysplasia with the prevalence of 1/60,000 approximatelyJu It is characterized by short limbs, short ribs, postaxial polydactyly, dysplastic nails/teeth, and congenital heart defects (CHD) which were observed in about 60% of affected individuals. Mutations in genes EHCoF EVC2 have been identified in two-thirds of patients with EvC syndrome.展开更多
基金the Korean Research Foundation(NRF-2021R1A2C3014067,NRF-RS-2023-00207857 to Murim Choi,NRF-2020R1A2C3006535,NRF-RS-2025-00519956 to Se-Hoon Lee)the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(HR20C0025 to Se-Hoon Lee)Future Medicine 20*30 Project of the Samsung Medical Center(SMX1230041 to Se-Hoon Lee).
文摘While immune checkpoint inhibitors(ICIs)are adopted as standard therapy for advanced non-small cell lung cancer(NSCLC),genetic determinants of response heterogeneity remain elusive[1].As most hematopoietic lineages undergo dynamic changes during tumor pathogenesis and immunotherapy[2],elucidating how germline variants modulate their transcriptomes is critical.Expression quantitative trait loci(eQTL)analysis,especially integrated with single-cell RNA sequencing(scRNA-seq),enables gene regulation mapping at single-cell resolution[3,4].Detailed methodologies are described in the Supplementary Materials.
文摘Background： The dilemma of pathogens identification in patients with unidentified clinical symptoms such as lever of unknown origin exists, which not only poses a challenge to both the diagnostic and therapeutic process by itself, but also to expert physicians. Methods： In this report, we have attempted to increase the awareness of unidentified pathogens by developing a method to investigate hitherto unidentified infectious pathogens based on unbiased high-throughput sequencing. Results： Our observations show that this method supplements current diagnostic technology that predominantly relies on information derived five cases from the intensive care unit. This methodological approach detects viruses and corrects the incidence of false positive detection rates of pathogens in a much shorter period. Through our method is followed by polymerase chain reaction validation, we could identify infection with Epstein-Barr virus, and in another case, we could identify infection with Streptococcus viridians based on the culture, which was false positive. Conclusions： This technology is a promising approach to revolutionize rapid diagnosis of infectious pathogens and to guide therapy that might result in the improvement of personalized medicine.
文摘Background： Congenital cataract （CC） is the leading cause of visual impairment or blindness in children worldwide. Because of highly genetic and clinical heterogeneity, a molecular diagnosis of the lens disease remains a challenge. Methods： In this study, we tested a three-generation Chinese family with autosomal dominant CCs by targeted sequencing of 45 CC genes on next generation sequencing and evaluated the pathogenicity of the detected mutation by protein structure, pedigree validation, and molecular dynamics （MD） simulation. Results： A novel 15 bp deletion on GJA8 （c.426_440delGCTGGAGGGGACCCT or p. 143147delLEGTL） was detected in the family. The deletion, concerned with an in-frame deletion of 5 amino acid residues in a highly evolutionarily conserved region within the cytoplasmic loop domain of the gap junction channel protein connexin 50 （CxS0）, was in full cosegregation with the cataract phenotypes in the family but not found in 1100 control exomes. MD simulation revealed that the introduction of the deletion destabilized the Cx50 gap junction channel, indicating the deletion as a dominant-negative mutation, Conclusions： The above results support the pathogenic role of the 15 bp deletion on GJA8 in the Chinese family and demonstrate targeted genes sequencing as a resolution to molecular diagnosis of CCs.
基金This study was supported by a grant from Beijing Key Laboratory of Maternal-Fetal Medicine in Fetal Heart Disease (No.BZ0308).
文摘To the Editor: Ellis van Creveld (EvC) syndrome is a rare, autosomal recessive skeletal dysplasia with the prevalence of 1/60,000 approximatelyJu It is characterized by short limbs, short ribs, postaxial polydactyly, dysplastic nails/teeth, and congenital heart defects (CHD) which were observed in about 60% of affected individuals. Mutations in genes EHCoF EVC2 have been identified in two-thirds of patients with EvC syndrome.
