Shengyuan Dang

All Publications

• Sequencing-free whole-genome spatial transcriptomics at single-molecule resolution. Cell Cheng, Y., Dang, S., Zhang, Y., Chen, Y., Yu, R., Liu, M., Jin, S., Han, A., Katz, S., Wang, S. 2025; 188 (24): 6953-6970.e12

  Abstract

  Recent breakthroughs in spatial transcriptomics technologies have enhanced our understanding of diverse cellular identities, spatial organizations, and functions. Yet existing spatial transcriptomics tools are still limited in either transcriptomic coverage or spatial resolution, hindering unbiased, hypothesis-free transcriptomic analyses at high spatial resolution. Here, we develop reverse-padlock amplicon-encoding fluorescence in situ hybridization (RAEFISH), an image-based spatial transcriptomics method with whole-genome coverage and single-molecule resolution in intact tissues. We demonstrate the spatial profiling of transcripts from 23,000 human or 22,000 mouse genes in single cells and tissue sections. Our analyses reveal transcript-specific subcellular localization, cell-type-specific and cell-type-invariant zonation-dependent transcriptomes, and gene programs underlying preferential cell-cell interactions. Finally, we further develop our technology for the direct spatial readout of guide RNAs (gRNAs) in an image-based, high-content CRISPR screen. Overall, these developments offer a broadly applicable technology that enables high-coverage, high-resolution spatial profiling of both long and short, native and engineered RNAs in many biomedical contexts.

  View details for DOI 10.1016/j.cell.2025.09.006

  View details for PubMedID 41038164

  View details for PubMedCentralID PMC12662569

• Temporal dynamics of SARS-CoV-2 genome mutations that occurred in vivo on an aircraft. Biosafety and health He, Y., Dang, S., Ma, W., Chen, L., Zhang, R., Mei, S., Wei, X., Lv, Q., Peng, B., Sun, Y., Kong, D., Chen, J., Li, S., Tang, X., Lu, Q., Zhu, C., Chen, Z., Wan, J., Zou, X., Li, M., Feng, T., Ren, L., Wang, J. 2023; 5 (1): 62-67

  Abstract

  We analyzed variations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome during a flight-related cluster outbreak of coronavirus disease 2019 (COVID-19) in Shenzhen, China, to explore the characteristics of SARS-CoV-2 transmission and intra-host single nucleotide variations (iSNVs) in a confined space. Thirty-three patients with COVID-19 were sampled, and 14 were resampled 3-31 days later. All 47 nasopharyngeal swabs were deep-sequenced. iSNVs and similarities in the consensus genome sequence were analyzed. Three SARS-CoV-2 variants of concern, Delta (n = 31), Beta (n = 1), and C.1.2 (n = 1), were detected among the 33 patients. The viral genome sequences from 30 Delta-positive patients had similar SNVs; 14 of these patients provided two successive samples. Overall, the 47 sequenced genomes contained 164 iSNVs. Of the 14 paired (successive) samples, the second samples (T2) contained more iSNVs (median: 3; 95% confidence interval [95% CI]: 2.77-10.22) than did the first samples (T1; median: 2; 95% CI: 1.63-3.74; Wilcoxon test, P = 0.021). 38 iSNVs were detected in T1 samples, and only seven were also detectable in T2 samples. Notably, T2 samples from two of the 14 paired samples had additional mutations than the T1 samples. The iSNVs of the SARS-CoV-2 genome exhibited rapid dynamic changes during a flight-related cluster outbreak event. Intra-host diversity increased gradually with time, and new site mutations occurred in vivo without a population transmission bottleneck. Therefore, we could not determine the generational relationship from the mutation site changes alone.

  View details for DOI 10.1016/j.bsheal.2022.10.004

  View details for PubMedID 36320662

  View details for PubMedCentralID PMC9613807

• Possible recombination between two variants of concern in a COVID-19 patient. Emerging microbes & infections He, Y., Ma, W., Dang, S., Chen, L., Zhang, R., Mei, S., Wei, X., Lv, Q., Peng, B., Chen, J., Kong, D., Sun, Y., Tang, X., Wu, W., Chen, Z., Li, S., Wan, J., Zou, X., Li, M., Feng, T., Ren, L., Wang, J. 2022; 11 (1): 552-555

  Abstract

  We identified an individual who was coinfected with two SARS-CoV-2 variants of concern, the Beta and Delta variants. The ratio of the relative abundance between the two variants was maintained at 1:9 (Beta:Delta) in 14 days. Furthermore, possible evidence of recombinations in the Orf1ab and Spike genes was found.

  View details for DOI 10.1080/22221751.2022.2032375

  View details for PubMedID 35081877

  View details for PubMedCentralID PMC8843165

• Functional mutations of SARS-CoV-2: implications to viral transmission, pathogenicity and immune escape. Chinese medical journal Dang, S., Ren, L., Wang, J. 2022; 135 (10): 1213-1222

  Abstract

  The pandemic of coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to major public health challenges globally. The increasing viral lineages identified indicate that the SARS-CoV-2 genome is evolving at a rapid rate. Viral genomic mutations may cause antigenic drift or shift, which are important ways by which SARS-CoV-2 escapes the human immune system and changes its transmissibility and virulence. Herein, we summarize the functional mutations in SARS-CoV-2 genomes to characterize its adaptive evolution to inform the development of vaccination, treatment as well as control and intervention measures.

  View details for DOI 10.1097/CM9.0000000000002158

  View details for PubMedID 35788093

  View details for PubMedCentralID PMC9337262

• Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19). Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Guo, L., Ren, L., Yang, S., Xiao, M., Chang, D., Yang, F., Dela Cruz, C. S., Wang, Y., Wu, C., Xiao, Y., Zhang, L., Han, L., Dang, S., Xu, Y., Yang, Q. W., Xu, S. Y., Zhu, H. D., Xu, Y. C., Jin, Q., Sharma, L., Wang, L., Wang, J. 2020; 71 (15): 778-785

  Abstract

  The emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. The current method of detection involves a quantitative polymerase chain reaction (qPCR)-based technique, which identifies the viral nucleic acids when present in sufficient quantity. False-negative results can be achieved and failure to quarantine the infected patient would be a major setback in containing the viral transmission. We aim to describe the time kinetics of various antibodies produced against the 2019 novel coronavirus (SARS-CoV-2) and evaluate the potential of antibody testing to diagnose COVID-19.The host humoral response against SARS-CoV-2, including IgA, IgM, and IgG response, was examined by using an ELISA-based assay on the recombinant viral nucleocapsid protein. 208 plasma samples were collected from 82 confirmed and 58 probable cases (qPCR negative but with typical manifestation). The diagnostic value of IgM was evaluated in this cohort.The median duration of IgM and IgA antibody detection was 5 (IQR, 3-6) days, while IgG was detected 14 (IQR, 10-18) days after symptom onset, with a positive rate of 85.4%, 92.7%, and 77.9%, respectively. In confirmed and probable cases, the positive rates of IgM antibodies were 75.6% and 93.1%, respectively. The detection efficiency by IgM ELISA is higher than that of qPCR after 5.5 days of symptom onset. The positive detection rate is significantly increased (98.6%) when combining IgM ELISA assay with PCR for each patient compared with a single qPCR test (51.9%).The humoral response to SARS-CoV-2 can aid in the diagnosis of COVID-19, including subclinical cases.

  View details for DOI 10.1093/cid/ciaa310

  View details for PubMedID 32198501

  View details for PubMedCentralID PMC7184472