Single-cell computational/system immunology (SCCI)
Single-cell analysis technologies such as single-cell RNA-sequencing and mass cytometry allow for measurements of cellular heterogeneity with unprecedented dimensionality. We focus on developing innovative single-cell data analytic methodologies to delineate immune cell subsets, detect rare cells, map immune cell lineage development and identify regulators of cell fate, trace cell trafficking, infer spatial localization and reconstruct cell-cell contact/interaction complex between different subsets of host immune cells, pathogens and malignant cells. We are interested in both method development and biological analysis.
Selected methods developed by our lab
· DensVM: automates cell subset identification and visualization (applicable to mass/flow cytometry data).
· Mpath: maps multi-branching single-cell trajectories of immune cell lineage development (applicable to single-cell RNA-seq, mass/flow cytometry data).
· Automated gating system for large flow cytometry datasets.
Applied to mass cytometry data, DensVM algorithm reveals the complexity of mouse myeloid cell compartment.
Applied to single-cell RNA-seq data of mouse conventional dendritic cell (cDC) progenitors, Mpath algorithm constructed multi-branching trajectories spanning from macrophage DC progenitors through common DC progenitor to pre-dendritic cells (preDC). The Mpath generated trajectories detected a branching event at the preDC stage revealing preDC subsets that were exclusively committed to cDC1 or cDC2 lineages, as well as novel early regulators of lineage commitment. Re-ordering cells along cDC developmental trajectories revealed sequential waves of gene regulation and temporal coupling between cell cycle and cDC differentiation.
· Jinmiao Chen, Andreas Schlitzer, Florent Ginhoux, Michael Poidinger, “Mpath maps multi-branching single-cell trajectories revealing progenitor cell progression during development” (co-corresponding author) (under review)
· Andreas Schlitzer, Sivakamasundari V*, Jinmiao Chen*, Hermi Rizal Bin Sumatoh, Jaring Schreuder, Josephine Lum, Benoit Malleret, Sanqian Zhang, Anis Larbi, Francesca Zolezzi, Laurent Renia, Michael Poidinger, Shalin Naik, Evan Newell, Paul Robson and Florent Ginhoux ,"Identification of subset-specific dendritic cell progenitors reveals early commitment in the bone marrow", Nature Immunology, vol. 16, pp. 718-728, 2015 (IF=24.97)
· Michael T Wong1*, Jinmiao Chen1*, Sriram Narayanan1, Wenyu Lin1, Rosslyn Anicete2, Henry Tan Kun Kiaang2, Maria Alicia Curotto De Lafaille1, Michael Poidinger1, Evan W. Newell. "Mapping the diversity and phenotypic progression of follicular helper T cells in human blood and tonsils using high dimensional mass cytometry analysis", Cell Reports, Volume 11, Issue 11, p1822-1833, 2015 (co-first author) (IF= 8.36)
· Guillaume Hoeffel, Jinmiao Chen, Yonit Lavin, Donovan Low, Francisca F. Almeida, Peter See, Anna E. Beaudin, Josephine Lum, Ivy Low, E. Camilla Forsberg, Michael Poidinger, Francesca Zolezzi, Anis Larbi, Lai Guan Ng, Jerry K.Y. Chan, Melanie Greter, Burkhard Becher, Igor M.
Samokhvalov, Miriam Merad, Ginhoux Florent. “C-Myb+ Erythro-Myeloid Progenitor-Derived Fetal Monocytes Give Rise to Adult Tissue-Resident Macrophages”, Immunity 04/2015; 42(4), pp 665–678 (IF=19.7)
· Valerie Chew, Marta Garnelo, Zhi Sheng Her, Chun Jye Lim, Alex Tan, Jinmiao Chen, Kiat Hon Lim, Achim Weber, Alexander Chung, London Lucien P.J. Ooi, Han Chong Toh, Mathias Heikenwalder, Irene O. L. Ng, Alessandra Nardin, Qing Feng Chen, Jean-Pierre Abastado. “Interaction between tumor-infiltrating B cells and T cells controls the progression of hepatocellular carcinoma”, Gut 2015 (IF=13.32)
· Irina N Shalova, Jyue Yuan Lim, Manesh Chittezhath, Annelies S Zinkernagel, Federico Beasley, Enrique Hernández-Jiménez, Victor Toledano, Carolina Cubillos-Zapata, Annamaria Rapisarda, Jinmiao Chen, Kaibo Duan, Henry Yang, Michael Poidinger, Giovanni Melillo, Victor Nizet, Francisco Arnalich, Eduardo López-Collazo, Subhra K Biswas, "Human Monocytes Undergo Functional Re-programming during Sepsis Mediated by Hypoxia-Inducible Factor-1α", Immunity 02/2015 (IF=19.7)
· Joan Hui Juan Lim, Sharada Ravikumar, Yan-Ming Wang, Thomas Paulraj Thamboo, Lizhen Ong, Jinmiao Chen, Jessamine Geraldine Goh, Sen Hee Tay, Lufei Chengchen, Mar Soe Win, [......], Roger Foo, Haris Mirza, Kevin Shyong Wei Tan, Sunil Sethi, Ai Leng Khoo, Wee Joo Chng, Osato Motomi, Mihai G Netea, Yue Wang, Louis Yi Ann Chai, "Bimodal Influence of Vitamin D in Host Response to Systemic Candida Infection - Vitamin D Dose Matters ", The Journal of Infectious Diseases 01/2015 (IF=5.78)
· Truong‐Minh Dang, Wing‐Cheong Wong, Siew‐Min Ong, Peng Li, Josephine Lum, Jinmiao Chen, Michael Poidinger, Francesca Zolezzi, Siew‐Cheng Wong, "MicroRNA expression profiling of human blood monocyte subsets highlights functional differences", Immunology 02/2015 (IF=3.8)
· Yuan Hong Yu, Gunaseelan Narayanan, Shvetha Sankaran, Srinivas Ramasamy, Shi Yu Chan, Shuping Lin, Jinmiao Chen, Henry Yang, Hariharan Srivats, Sohail Ahmed, “Purification, visualisation and molecular signature of neural stem cells”, Stem cells and development 10/2015 (IF=3.73)
· Fabien Cottier, Alrina Shin Min Tan, Jinmiao Chen, Josephine Lum, Francesca Zolezzi, Michael Poidinger, Norman Pavelka, "The Transcriptional Stress Response of Candida albicans to Weak Organic Acids", G3-Genes Genomes Genetics, 01/2015 (IF=2.51)
· B. Becher*, A. Schlitzer*, J. Chen*, F. Mair, H. Sumatoh, K. Teng, D. Low, C. Ruedl, P. Riccardi-Castagnoli, M. Poidinger, M. Greter, F. Ginhoux, and E. W. Newell, "High dimensional analysis of the murine myeloid cell system" Nature Immunology, vol. 15(12), pp. 1181-9, 2014 (co-first author) (IF=24.97).
· J. Chen, Y. Xue, M. Poidinger, T. Lim, S. H. Chew, C. L. Pang, J. P. Abastado, and F. Thierry, "Mapping of HPV transcripts in four human cervical lesions using RNAseq suggests quantitative rearrangements during carcinogenic progression," Virology, vol. 462-463, pp. 14-24, Aug 2014 (IF=3.28)
· J. Fric, C. X. Lim, A. Mertes, B. T. Lee, E. Vigano, J. Chen, F. Zolezzi, M. Poidinger, A. Larbi, H. Strobl, T. Zelante, and P. Ricciardi-Castagnoli, "Calcium and Calcineurin-Nfat Signaling Regulate Granulocyte-Monocyte Progenitor Cell cycle Via Flt3-L," Stem Cells, Aug 7 2014 (IF=7.7)
· Manesh Chittezhath, Manprit Kaur Dhillon, Jyue Yuan Lim, Damya Laoui, Irina N Shalova, Yi Ling Teo, Jinmiao Chen, Revathy Kamaraj, Lata Raman, Josephine Lum, Thomas Paulraj Thamboo, Edmund Chiong, Francesca Zolezzi, Henry Yang, Jo A Van Ginderachter, Michael Poidinger, Alvin S C Wong, Subhra K Biswas, Molecular profiling reveals a tumor-promoting phenotype of monocytes and macrophages in human cancer progression. Immunity 11/2014 (IF=19.75)
· Amit Singhal, Liu Jie, Pavanish Kumar, Gan Suay Hong, Melvin Khee-Shing Leow, Bhairav Paleja, Liana Tsenova, Natalia Kurepina, Jinmiao Chen, Francesca Zolezzi, Barry Kreiswirth, Michael Poidinger, Cynthia Chee, Gilla Kaplan, Yee Tang Wang, Gennaro De Libero, Metformin as adjunct antituberculosis therapy, Science translational medicine 11/2014 (IF=14.41)
· Sébastien Calbo, Xavier Camous, Baptiste Janela, Kim Périchon, Jinmiao Chen, Edmond Chua, Josephine Lum, Francesca Zolezzi, Michael Poidinger, Philippe Musette, Gene profiling of B lymphoblastoid cell lines from DRESS patients after drugs incubation, Clinical and Translational Allergy 07/2014
· Mertes Alexandra, Fric Jan, Lim Clarice, Tay Hock Soon, Zelante Teresa, Chen Jinmiao, Ricciardi-Castagnoli Paola, “Role of calcineurin/NFAT signalling in myeloid cell haematopoiesis and function”, Frontiers in Immunology 01/2013
· M. Ang, G. Cheung, M. Vania, J. Chen, H. Yang, J. Li, and S. P. Chee, "Aqueous cytokine and chemokine analysis in uveitis associated with tuberculosis," Mol Vis, vol. 18, pp. 565-73, 2012.
· V. Chew, J. Chen, D. Lee, E. Loh, J. Lee, K. H. Lim, A. Weber, K. Slankamenac, R. T. Poon, H. Yang, L. L. Ooi, H. C. Toh, M. Heikenwalder, I. O. Ng, A. Nardin, and J. P. Abastado, "Chemokine-driven lymphocyte infiltration: an early intratumoural event determining long-term survival in resectable hepatocellular carcinoma," Gut, vol. 61, pp. 427-38, Mar 2012 (IF=13.32)
· J. Fric, C. X. Lim, E. G. Koh, B. Hofmann, J. Chen, H. S. Tay, S. A. Mohammad Isa, A. Mortellaro, C. Ruedl, and P. Ricciardi-Castagnoli, "Calcineurin/NFAT signalling inhibits myeloid haematopoiesis," EMBO Mol Med, vol. 4, pp. 269-82, Apr 2012 (IF=8.25)
· G. Narayanan, A. Poonepalli, J. Chen, S. Sankaran, S. Hariharan, Y. H. Yu, P. Robson, H. Yang, and S. Ahmed, "Single-cell mRNA profiling identifies progenitor subclasses in neurospheres," Stem Cells Dev, vol. 21, pp. 3351-62, Dec 10 2012 (IF=4.2)
· Chow, Z. Her, E. K. Ong, J. M. Chen, F. Dimatatac, D. J. Kwek, T. Barkham, H. Yang, L. Renia, Y. S. Leo, and L. F. Ng, "Persistent arthralgia induced by Chikungunya virus infection is associated with interleukin-6 and granulocyte macrophage colony-stimulating factor," J Infect Dis, vol. 203, pp. 149-57, Jan 15 2011 (IF=5.78).
· G. Maubach, M. C. Lim, J. Chen, H. Yang, and L. Zhuo, "miRNA studies in in vitro and in vivo activated hepatic stellate cells," World J Gastroenterol,vol. 17, pp. 2748-73, Jun 14 2011.
2009 and before
· J. Chen and N. S. Chaudhari, "Segmented-memory recurrent neural networks," IEEE Trans Neural Network, vol. 20, pp. 1267-80, Aug 2009.
· J. Chen and N. Chaudhari, "Cascaded bidirectional recurrent neural networks for protein secondary structure prediction," IEEE/ACM Trans Comput Biol Bioinform, vol. 4, pp. 572-82, Oct-Dec 2007.
· J. Chen and N. S. Chaudhari, "Bidirectional segmented-memory recurrent neural network for protein secondary structure prediction," Soft Computing, vol. 10, pp. 315-324, 2006.