Stanford Advisors

All Publications

  • Identification of novel single nucleotide variants in the drug resistance mechanism of Mycobacterium tuberculosis isolates by whole-genome analysis. BMC genomics Qian, W., Ma, N., Zeng, X., Shi, M., Wang, M., Yang, Z., Tsui, S. K. 2024; 25 (1): 478


    BACKGROUND: Tuberculosis (TB) represents a major global health challenge. Drug resistance in Mycobacterium tuberculosis (MTB) poses a substantial obstacle to effective TB treatment. Identifying genomic mutations in MTB isolates holds promise for unraveling the underlying mechanisms of drug resistance in this bacterium.METHODS: In this study, we investigated the roles of single nucleotide variants (SNVs) in MTB isolates resistant to four antibiotics (moxifloxacin, ofloxacin, amikacin, and capreomycin) through whole-genome analysis. We identified the drug-resistance-associated SNVs by comparing the genomes of MTB isolates with reference genomes using the MuMmer4 tool.RESULTS: We observed a strikingly high proportion (94.2%) of MTB isolates resistant to ofloxacin, underscoring the current prevalence of drug resistance in MTB. An average of 3529 SNVs were detected in a single ofloxacin-resistant isolate, indicating a mutation rate of approximately 0.08% under the selective pressure of ofloxacin exposure. We identified a set of 60 SNVs associated with extensively drug-resistant tuberculosis (XDR-TB), among which 42 SNVs were non-synonymous mutations located in the coding regions of nine key genes (ctpI, desA3, mce1R, moeB1, ndhA, PE_PGRS4, PPE18, rpsA, secF). Protein structure modeling revealed that SNVs of three genes (PE_PGRS4, desA3, secF) are close to the critical catalytic active sites in the three-dimensional structure of the coding proteins.CONCLUSION: This comprehensive study elucidates novel resistance mechanisms in MTB against antibiotics, paving the way for future design and development of anti-tuberculosis drugs.

    View details for DOI 10.1186/s12864-024-10390-3

    View details for PubMedID 38745294

  • Modeling ionizing radiation-induced cardiovascular dysfunction with human iPSC-derived engineered heart tissues. Journal of molecular and cellular cardiology Cao, X., Thomas, D., Whitcomb, L. A., Wang, M., Chatterjee, A., Chicco, A. J., Weil, M. M., Wu, J. C. 2024; 188: 105-107

    View details for DOI 10.1016/j.yjmcc.2023.11.012

    View details for PubMedID 38431383

  • Genomic analysis reveals novel allergens of Blomia tropicalis. Allergology international : official journal of the Japanese Society of Allergology Xiong, Q., Liu, X., Wan, A. T., Malainual, N., Xiao, X., Cao, H., Tang, M. F., Ng, J. K., Shin, S. K., Sio, Y. Y., Wang, M., Sun, B., Leung, T. F., Chew, F. T., Tungtrongchitr, A., Tsui, S. K. 2023

    View details for DOI 10.1016/j.alit.2023.11.004

    View details for PubMedID 38061933

  • Multi-omic analysis of Tyrophagus putrescentiae reveals insights into the allergen complexity of storage mites. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology Wan, A. T., Xiong, Q., Xiao, X., Ao, K. F., Jang, S. W., Wong, B. S., Wang, M., Cao, Q., Fung, C. S., Chew, F. T., Sun, B., Ngai, S. M., Leung, T. F., Jeong, K. Y., Liu, X., Tsui, S. K. 2023

    View details for DOI 10.1111/cea.14418

    View details for PubMedID 37984814

  • MitoTrace: A Computational Framework for Analyzing Mitochondrial Variation in Single-Cell RNA Sequencing Data. Genes Wang, M., Deng, W., Samuels, D. C., Zhao, Z., Simon, L. M. 2023; 14 (6)


    Genetic variation in the mitochondrial genome is linked to important biological functions and various human diseases. Recent progress in single-cell genomics has established single-cell RNA sequencing (scRNAseq) as a popular and powerful technique to profile transcriptomics at the cellular level. While most studies focus on deciphering gene expression, polymorphisms including mitochondrial variants can also be readily inferred from scRNAseq. However, limited attention has been paid to investigate the single-cell landscape of mitochondrial variants, despite the rapid accumulation of scRNAseq data in the community. In addition, a diploid context is assumed for most variant calling tools, which is not appropriate for mitochondrial heteroplasmies. Here, we introduce MitoTrace, an R package for the analysis of mitochondrial genetic variation in bulk and scRNAseq data. We applied MitoTrace to several publicly accessible data sets and demonstrated its ability to robustly recover genetic variants from scRNAseq data. We also validated the applicability of MitoTrace to scRNAseq data from diverse platforms. Overall, MitoTrace is a powerful and user-friendly tool to investigate mitochondrial variants from scRNAseq data.

    View details for DOI 10.3390/genes14061222

    View details for PubMedID 37372402

    View details for PubMedCentralID PMC10298143

  • Exercise reprograms the inflammatory landscape of multiple stem cell compartments during mammalian aging. Cell stem cell Liu, L., Kim, S., Buckley, M. T., Reyes, J. M., Kang, J., Tian, L., Wang, M., Lieu, A., Mao, M., Rodriguez-Mateo, C., Ishak, H. D., Jeong, M., Wu, J. C., Goodell, M. A., Brunet, A., Rando, T. A. 2023


    Exercise has the ability to rejuvenate stem cells and improve tissue regeneration in aging animals. However, the cellular and molecular changes elicited by exercise have not been systematically studied across a broad range of cell types in stem cell compartments. We subjected young and old mice to aerobic exercise and generated a single-cell transcriptomic atlas of muscle, neural, and hematopoietic stem cells with their niche cells and progeny, complemented by whole transcriptome analysis of single myofibers. We found that exercise ameliorated the upregulation of a number of inflammatory pathways associated with old age and restored aspects of intercellular communication mediated by immune cells within these stem cell compartments. Exercise has a profound impact on the composition and transcriptomic landscape of circulating and tissue-resident immune cells. Our study provides a comprehensive view of the coordinated responses of multiple aged stem cells and niche cells to exercise at the transcriptomic level.

    View details for DOI 10.1016/j.stem.2023.03.016

    View details for PubMedID 37080206

  • Genomic Analysis of Amphioxus Reveals a Wide Range of Fragments Homologous to Viral Sequences. Viruses Du, Q., Peng, F., Xiong, Q., Xu, K., Yang, K. Y., Wang, M., Wu, Z., Li, S., Cheng, X., Rao, X., Wang, Y., Tsui, S. K., Zeng, X. 2023; 15 (4)


    Amphioxus species are considered living fossils and are important in the evolutionary study of chordates and vertebrates. To explore viral homologous sequences, a high-quality annotated genome of the Beihai amphioxus (Branchiostoma belcheri beihai) was examined using virus sequence queries. In this study, 347 homologous fragments (HFs) of viruses were identified in the genome of B. belcheri beihai, of which most were observed on 21 genome assembly scaffolds. HFs were preferentially located within protein-coding genes, particularly in their CDS regions and promoters. A range of amphioxus genes with a high frequency of HFs is proposed, including histone-related genes that are homologous to the Histone or Histone H2B domains of viruses. Together, this comprehensive analysis of viral HFs provides insights into the neglected role of viral integration in the evolution of amphioxus.

    View details for DOI 10.3390/v15040909

    View details for PubMedID 37112889

  • Endogenous Plasmids and Chromosomal Genome Reduction in the Cardinium Endosymbiont of Dermatophagoides farinae. mSphere Xiong, Q., Fung, C. S., Xiao, X., Wan, A. T., Wang, M., Klimov, P., Ren, Y., Yang, K. Y., Hubert, J., Cui, Y., Liu, X., Tsui, S. K. 2023: e0007423


    Cardinium bacteria are well known as endosymbionts that infect a wide range of arthropods and can manipulate host reproduction to promote their vertical transmission. As intracellular bacteria, Cardinium species undergo dramatic genome evolution, especially their chromosomal genome reduction. Although Cardinium plasmids have been reported to harbor important genes, the role of these plasmids in the genome evolution is yet to be fully understood. In this study, 2 genomes of Cardinium endosymbiont bacteria in astigmatic mites were de novo assembled, including the complete circular chromosomal genome of Cardinium sp. DF that was constructed in high quality using high-coverage long-read sequencing data. Intriguingly, 2 circular plasmids were assembled in Cardinium sp. DF and were identified to be endogenous for over 10 homologous genes shared with the chromosomal genome. Comparative genomics analysis illustrated an outline of the genome evolution of Cardinium bacteria, and the in-depth analysis of Cardinium sp. DF shed light on the multiple roles of endogenous plasmids in the molecular process of the chromosomal genome reduction. The endogenous plasmids of Cardinium sp. DF not only harbor massive homologous sequences that enable homologous recombination with the chromosome, but also can provide necessary functional proteins when the coding genes decayed in the chromosomal genome. IMPORTANCE As bacterial endosymbionts, Cardinium typically undergoes genome reduction, but the molecular process is still unclear, such as how plasmids get involved in chromosome reduction. Here, we de novo assembled 2 genomes of Cardinium in astigmatic mites, especially the chromosome of Cardinium sp. DF was assembled in a complete circular DNA using high-coverage long-read sequencing data. In the genome assembly of Cardinium sp. DF, 2 circular endogenous plasmids were identified to share at least 10 homologous genes with the chromosomal genome. In the comparative analysis, we identified a range of genes decayed in the chromosomal genome of Cardinium sp. DF but preserved in the 2 plasmids. Taken together with in-depth analyses, our results unveil that the endogenous plasmids harbor homologous sequences of chromosomal genome and can provide a structural basis of homologous recombination. Overall, this study reveals that endogenous plasmids participate in the ongoing chromosomal genome reduction of Cardinium sp. DF.

    View details for DOI 10.1128/msphere.00074-23

    View details for PubMedID 36939349

  • Optimized Hybrid Deep Learning for Real-Time Pandemic Data Forecasting: Long and Short-Term Perspectives Current Bioinformatics Dash, S., Giri, S., Pani, S., Mallik, S., Wang, M., Qin, H. 2023
  • Comparative Genomics Reveals Insights into the Divergent Evolution of Astigmatic Mites and Household Pest Adaptations. Molecular biology and evolution Xiong, Q., Wan, A. T., Liu, X., Fung, C. S., Xiao, X., Malainual, N., Hou, J., Wang, L., Wang, M., Yang, K. Y., Cui, Y., Leung, E. L., Nong, W., Shin, S. K., Au, S. W., Jeong, K. Y., Chew, F. T., Hui, J. H., Leung, T. F., Tungtrongchitr, A., Zhong, N., Liu, Z., Tsui, S. K. 2022; 39 (5)


    Highly diversified astigmatic mites comprise many medically important human household pests such as house dust mites causing ∼1-2% of all allergic diseases globally; however, their evolutionary origin and diverse lifestyles including reversible parasitism have not been illustrated at the genomic level, which hampers allergy prevention and our exploration of these household pests. Using six high-quality assembled and annotated genomes, this study not only refuted the monophyly of mites and ticks, but also thoroughly explored the divergence of Acariformes and the diversification of astigmatic mites. In monophyletic Acariformes, Prostigmata known as notorious plant pests first evolved, and then rapidly evolving Astigmata diverged from soil oribatid mites. Within astigmatic mites, a wide range of gene families rapidly expanded via tandem gene duplications, including ionotropic glutamate receptors, triacylglycerol lipases, serine proteases and UDP glucuronosyltransferases. Gene diversification after tandem duplications provides many genetic resources for adaptation to sensing environmental signals, digestion, and detoxification in rapidly changing household environments. Many gene decay events only occurred in the skin-burrowing parasitic mite Sarcoptes scabiei. Throughout the evolution of Acariformes, massive horizontal gene transfer events occurred in gene families such as UDP glucuronosyltransferases and several important fungal cell wall lytic enzymes, which enable detoxification and digestive functions and provide perfect drug targets for pest control. This comparative study sheds light on the divergent evolution and quick adaptation to human household environments of astigmatic mites and provides insights into the genetic adaptations and even control of human household pests.

    View details for DOI 10.1093/molbev/msac097

    View details for PubMedID 35535514

  • Single-Cell RNA Sequencing (scRNA-seq) in Cardiac Tissue: Applications and Limitations. Vascular health and risk management Wang, M., Gu, M., Liu, L., Liu, Y., Tian, L. 2021; 17: 641-657


    Cardiovascular diseases (CVDs) are a group of disorders of the blood vessels and heart, which are considered as the leading causes of death worldwide. The pathology of CVDs could be related to the functional abnormalities of multiple cell types in the heart. Single-cell RNA sequencing (scRNA-seq) technology is a powerful method for characterizing individual cells and elucidating the molecular mechanisms by providing a high resolution of transcriptomic changes at the single-cell level. Specifically, scRNA-seq has provided novel insights into CVDs by identifying rare cardiac cell types, inferring the trajectory tree, estimating RNA velocity, elucidating the cell-cell communication, and comparing healthy and pathological heart samples. In this review, we summarize the different scRNA-seq platforms and published single-cell datasets in the cardiovascular field, and describe the utilities and limitations of this technology. Lastly, we discuss the future perspective of the application of scRNA-seq technology into cardiovascular research.

    View details for DOI 10.2147/VHRM.S288090

    View details for PubMedID 34629873

  • Endothelial-Myocardial Angiocrine Signaling in Heart Development. Frontiers in cell and developmental biology Kim, H., Wang, M., Paik, D. T. 2021; 9: 697130


    Vascular endothelial cells are a multifunctional cell type with organotypic specificity in their function and structure. In this review, we discuss various subpopulations of endothelial cells in the mammalian heart, which spatiotemporally regulate critical cellular and molecular processes of heart development via unique sets of angiocrine signaling pathways. In particular, elucidation of intercellular communication among the functional cell types in the developing heart has recently been accelerated by the use of single-cell sequencing. Specifically, we overview the heterogeneic nature of cardiac endothelial cells and their contribution to heart tube and chamber formation, myocardial trabeculation and compaction, and endocardial cushion and valve formation via angiocrine pathways.

    View details for DOI 10.3389/fcell.2021.697130

    View details for PubMedID 34277641

  • In silico analysis of proteins and microRNAs related to human African trypanosomiasis in tsetse fly COMPUTATIONAL BIOLOGY AND CHEMISTRY Yang, Z., Wang, M., Zeng, X., Wan, A., Tsui, S. 2020; 88: 107347


    Human African trypanosomiasis (HAT), also known as sleeping sickness, causes millions of deaths worldwide. HAT is primarily transmitted by the vector tsetse fly (Glossina morsitans). Early diagnosis remains a key objective for treating this disease. MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs that play key roles in vector-borne diseases. To date, the roles of proteins and miRNAs in HAT disease have not been thoroughly elucidated. In this study, we have re-annotated the function of protein-coding genes and identified several miRNAs based on a series of bioinformatics tools. A batch of 81.1 % of tsetse fly proteins could be determined homology in mosquito genome, suggesting their probable similar mechanisms in vector-borne diseases. A set of 11 novel salivary proteins and 14 midgut proteins were observed in the tsetse fly, which could be applied to the development of vaccine candidates for the control of HAT disease. In addition, 35 novel miRNAs were identified, among which 10 miRNAs were found to be unique in tsetse fly. Pathway analysis of these 10 miRNAs indicated that targets of miR-15a-5p were significantly enriched in the HAT-related neurotrophin signaling pathway. Besides, topological analysis of the miRNA-gene network indicated that miR-619-5p and miR-2490-3p targeted several genes that respond to trypanosome infection, including thioester-containing protein Tep1 and heat shock protein Hsp60a. In conclusion, our work helps to elucidate the function of miRNAs in tsetse fly and establishes a foundation for further investigations into the molecular regulatory mechanisms of HAT disease.

    View details for DOI 10.1016/j.compbiolchem.2020.107347

    View details for Web of Science ID 000591245400012

    View details for PubMedID 32745971

  • Systematic Design of Drug Repurposing-Oriented Alzheimer’s Disease Ontology 2019 IEEE International Conference on Healthcare Informatics (ICHI) Li, F., Wang, M., Pham , H., Tao, C., et al 2019
  • High-quality assembly of Dermatophagoides pteronyssinus genome and transcriptome reveals a wide range of novel allergens JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Liu, X., Yang, K., Wang, M., Kwok, J., Zeng, X., Yang, Z., Xiao, X., Lau, C., Li, Y., Huang, Z., Ba, J., Yim, A., Ouyang, C., Ngai, S., Chan, T., Leung, E., Liu, L., Liu, Z., Tsui, S. 2018; 141 (6): 2268-2271

    View details for DOI 10.1016/j.jaci.2017.11.038

    View details for Web of Science ID 000434701600031

    View details for PubMedID 29305317

  • High-quality assembly of Dermatophagoides pteronyssinus genome and transcriptome reveals a wide range of novel allergens Wan, A., Liu, X., Yang, K., Wang, M., Kwok, J., Zeng, X., Yang, Z., Xiao, X., Lau, C., Li, Y., Huang, Z., Ba, J., Yim, A., Ouyang, C., Ngai, S., Chan, T., Leung, E., Liu, L., Liu, Z., Tsui, S. MOSBY-ELSEVIER. 2018: AB286