Arthritis National Research Foundation, Deciphering complement-dependent phagocytic myeloid phenotypes in human autoimmune arthritis using single-cell computational omics
(2023)
Translational Research Scholar Program (TRSP) CU School of Medicine, Using AI to elucidate novel pathogenic programs underlying chronic inflammatory diseases for precision medicine
(2023)
CU Orthopedics-Department of Biomedical Informatics (DBMI) Dyads Award, Multi-Omics Integration with Machine Learning to Reveal Synovium Phenotypes in Ankle Osteoarthritis
(2023)
PhRMA Research Starter Grant, Deciphering shared inflammatory myeloid phenotypes between rheumatoid arthritis (RA) and RA-associated interstitial lung disease by Computational Omics
(2022)
Research Interests
We are a Computational Omics and Systems Immunology (COSI) lab https://fanzhanglab.org/ in the Department of Medicine Division of Rheumatology and the Department of the Biomedical Informatics Center for Health AI, University of Colorado Anschutz Campus.
We develop and use computational machine learning methods, single-cell multi-omics, and systems immunology approaches to study immune-mediated diseases.
Teaching
Lecture
(2023)
School of Medicine,
Biomedical Informatics
Computational Bioscience
Publications
Bai Z, Bartelo N, Aslam M, Murphy EA, Hale CR, Blachere NE, Parveen S, Spolaore E, DiCarlo E, Gravallese EM, Smith MH, Frank MO, Jiang CS, Zhang H, Pyrgaki C, Lewis MJ, Sikandar S, Pitzalis C, Lesnak JB, Mazhar K, Price TJ, Malfait AM, Miller RE, Zhang F, Goodman S, Darnell RB, Wang F, Orange DE. Synovial fibroblast gene expression is associated with sensory nerve growth and pain in rheumatoid arthritis. Sci Transl Med. 2024 Apr 10;16(742):eadk3506. PubMed PMID: 38598614
Davidson NR, Zhang F, Greene CS. BuDDI: Bulk Deconvolution with Domain Invariance to predict cell-type-specific perturbations from bulk. bioRxiv. 2024 Apr 4. PubMed PMID: 37503097
Dunlap G, Wagner A, Meednu N, Zhang F, Jonsson AH, Wei K, Sakaue S, Nathan A, Bykerk VP, Donlin LT, Goodman SM, Firestein GS, Boyle DL, Holers VM, Moreland LW, Tabechian D, Pitzalis C, Filer A, Raychaudhuri S, Brenner MB, McDavid A, Rao DA, Anolik JH. Clonal associations of lymphocyte subsets and functional states revealed by single cell antigen receptor profiling of T and B cells in rheumatoid arthritis synovium. bioRxiv. 2023 Mar 21. PubMed PMID: 36993527
Faust HJ, Cheng TY, Korsunsky I, Watts GFM, Gal-Oz ST, Trim W, Kongthong K, Jonsson AH, Simmons DP, Zhang F, Padera R, Chubinskaya S, Wei K, Raychaudhuri S, Lynch L, Moody DB, Brenner MB. Adipocytes regulate fibroblast function, and their loss contributes to fibroblast dysfunction in inflammatory diseases. bioRxiv. 2023 May 18. PubMed PMID: 37292637
Weinand K, Sakaue S, Nathan A, Jonsson AH, Zhang F, Watts GFM, Zhu Z, Rao DA, Anolik JH, Brenner MB, Donlin LT, Wei K, Raychaudhuri S. The Chromatin Landscape of Pathogenic Transcriptional Cell States in Rheumatoid Arthritis. bioRxiv. 2023 Apr 8. PubMed PMID: 37066336
Zhang F, Jonsson AH, Nathan A, Millard N, Curtis M, Xiao Q, Gutierrez-Arcelus M, Apruzzese W, Watts GFM, Weisenfeld D, Nayar S, Rangel-Moreno J, Meednu N, Marks KE, Mantel I, Kang JB, Rumker L, Mears J, Slowikowski K, Weinand K, Orange DE, Geraldino-Pardilla L, Deane KD, Tabechian D, Ceponis A, Firestein GS, Maybury M, Sahbudin I, Ben-Artzi A, Mandelin AM 2nd, Nerviani A, Lewis MJ, Rivellese F, Pitzalis C, Hughes LB, Horowitz D, DiCarlo E, Gravallese EM, Boyce BF, Moreland LW, Goodman SM, Perlman H, Holers VM, Liao KP, Filer A, Bykerk VP, Wei K, Rao DA, Donlin LT, Anolik JH, Brenner MB, Raychaudhuri S. Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes. Nature. 2023 Nov;623(7987):616-624. PubMed PMID: 37938773
Kang JB, Shen AZ, Gurajala S, Nathan A, Rumker L, Aguiar VRC, Valencia C, Lagattuta KA, Zhang F, Jonsson AH, Yazar S, Alquicira-Hernandez J, Khalili H, Ananthakrishnan AN, Jagadeesh K, Dey K, Daly MJ, Xavier RJ, Donlin LT, Anolik JH, Powell JE, Rao DA, Brenner MB, Gutierrez-Arcelus M, Luo Y, Sakaue S, Raychaudhuri S. Mapping the dynamic genetic regulatory architecture of HLA genes at single-cell resolution. Nat Genet. 2023 Dec;55(12):2255-2268. PubMed PMID: 38036787
Iijima H, Zhang F, Ambrosio F, Matsui Y. Network-based cytokine inference implicates Oncostatin M as a driver of an inflammation phenotype in knee osteoarthritis. Aging Cell. 2023 Dec 18;:e14043. [Epub ahead of print] PubMed PMID: 38111237
Weisenfeld D, Zhang F, Donlin L, Jonsson AH, Apruzzese W, Campbell D, Rao DA, Wei K, Holers VM, Gravallese E, Moreland L, Goodman S, Brenner M, Raychaudhuri S, Filer A, Anolik J, Bykerk V, Liao KP. Associations between rheumatoid arthritis clinical factors with synovial cell types and states. Arthritis Rheumatol. 2023 Oct 4. [Epub ahead of print] PubMed PMID: 37791989
Weisenfeld D, Zhang F, Donlin L, Jonsson AH, Apruzzese W, Campbell D, Rao DA, Wei K, Holers VM, Gravallese E, Moreland L, Goodman S, Brenner M, Raychaudhuri S, Filer A, Anolik J, Bykerk V, Liao KP. Associations between rheumatoid arthritis clinical factors with synovial cell types and states. Arthritis Rheumatol. 2023 Oct 4. [Epub ahead of print] PubMed PMID: 37791989
Zhang F, Jonsson AH, Nathan A, Millard N, Curtis M, Xiao Q, Gutierrez-Arcelus M, Apruzzese W, Watts GFM, Weisenfeld D, Nayar S, Rangel-Moreno J, Meednu N, Marks KE, Mantel I, Kang JB, Rumker L, Mears J, Slowikowski K, Weinand K, Orange DE, Geraldino-Pardilla L, Deane KD, Tabechian D, Ceponis A, Firestein GS, Maybury M, Sahbudin I, Ben-Artzi A, Mandelin AM 2nd, Nerviani A, Lewis MJ, Rivellese F, Pitzalis C, Hughes LB, Horowitz D, DiCarlo E, Gravallese EM, Boyce BF, Moreland LW, Goodman SM, Perlman H, Holers VM, Liao KP, Filer A, Bykerk VP, Wei K, Rao DA, Donlin LT, Anolik JH, Brenner MB, Raychaudhuri S. Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes. Nature. 2023 Nov;623(7987):616-624. PubMed PMID: 37938773
Kang JB, Shen AZ, Gurajala S, Nathan A, Rumker L, Aguiar VRC, Valencia C, Lagattuta KA, Zhang F, Jonsson AH, Yazar S, Alquicira-Hernandez J, Khalili H, Ananthakrishnan AN, Jagadeesh K, Dey K, Daly MJ, Xavier RJ, Donlin LT, Anolik JH, Powell JE, Rao DA, Brenner MB, Gutierrez-Arcelus M, Luo Y, Sakaue S, Raychaudhuri S. Mapping the dynamic genetic regulatory architecture of HLA genes at single-cell resolution. Nat Genet. 2023 Dec;55(12):2255-2268. PubMed PMID: 38036787
Iijima H, Zhang F, Ambrosio F, Matsui Y. Network-based cytokine inference implicates Oncostatin M as a driver of an inflammation phenotype in knee osteoarthritis. Aging Cell. 2023 Dec 18;:e14043. [Epub ahead of print] PubMed PMID: 38111237
Inamo J, Keegan J, Griffith A, Ghosh T, Horisberger A, Howard K, Pulford J, Murzin E, Hancock B, Jonsson AH, Seifert J, Feser ML, Norris JM, Cao Y, Apruzzese W, Louis Bridges S, Bykerk V, Goodman S, Donlin L, Firestein GS, Perlman H, Bathon JM, Hughes LB, Tabechian D, Filer A, Pitzalis C, Anolik JH, Moreland L, Guthridge JM, James JA, Brenner MB, Raychaudhuri S, Sparks JA, Michael Holers V, Deane KD, Lederer JA, Rao DA, Zhang F. Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis. bioRxiv. 2023 Jul 4. PubMed PMID: 37461737
Weinand K, Sakaue S, Nathan A, Jonsson AH, Zhang F, Watts GFM, Zhu Z, Rao DA, Anolik JH, Brenner MB, Donlin LT, Wei K, Raychaudhuri S. The Chromatin Landscape of Pathogenic Transcriptional Cell States in Rheumatoid Arthritis. bioRxiv. 2023 Apr 8. PubMed PMID: 37066336
Dunlap G, Wagner A, Meednu N, Zhang F, Jonsson AH, Wei K, Sakaue S, Nathan A, Bykerk VP, Donlin LT, Goodman SM, Firestein GS, Boyle DL, Holers VM, Moreland LW, Tabechian D, Pitzalis C, Filer A, Raychaudhuri S, Brenner MB, McDavid A, Rao DA, Anolik JH. Clonal associations of lymphocyte subsets and functional states revealed by single cell antigen receptor profiling of T and B cells in rheumatoid arthritis synovium. bioRxiv. 2023 Mar 21. PubMed PMID: 36993527
Guan S, Mehta B, Slater D, Thompson JR, DiCarlo E, Pannellini T, Pearce-Fisher D, Zhang F, Raychaudhuri S, Hale C, Jiang CS, Goodman S, Orange DE. Rheumatoid Arthritis Synovial Inflammation Quantification Using Computer Vision. ACR Open Rheumatol. 2022 Apr;4(4):322-331. PubMed PMID: 35014221
Meednu N, Rangel-Moreno J, Zhang F, Escalera-Rivera K, Corsiero E, Prediletto E, DiCarlo E, Goodman S, Donlin LT, Raychauduri S, Bombardieri M, Pitzalis C, Orange DE, McDavid A, Anolik JH. Dynamic spectrum of ectopic lymphoid B cell activation and hypermutation in the RA synovium characterized by NR4A nuclear receptor expression. Cell Rep. 2022 May 3;39(5):110766. PubMed PMID: 35508128
Jonsson AH, Zhang F, Dunlap G, Gomez-Rivas E, Watts GFM, Faust HJ, Rupani KV, Mears JR, Meednu N, Wang R, Keras G, Coblyn JS, Massarotti EM, Todd DJ, Anolik JH, McDavid A, Wei K, Rao DA, Raychaudhuri S, Brenner MB. Granzyme K( ) CD8 T cells form a core population in inflamed human tissue. Sci Transl Med. 2022 Jun 15;14(649):eabo0686. PubMed PMID: 35704599
Meednu N, Rangel-Moreno J, Zhang F, Escalera-Rivera K, Corsiero E, Prediletto E, DiCarlo E, Goodman S, Donlin LT, Raychauduri S, Bombardieri M, Pitzalis C, Orange DE, McDavid A, Anolik JH. Dynamic spectrum of ectopic lymphoid B cell activation and hypermutation in the RA synovium characterized by NR4A nuclear receptor expression. Cell Rep. 2022 May 3;39(5):110766. PubMed PMID: 35508128
Guan S, Mehta B, Slater D, Thompson JR, DiCarlo E, Pannellini T, Pearce-Fisher D, Zhang F, Raychaudhuri S, Hale C, Jiang CS, Goodman S, Orange DE. Rheumatoid Arthritis Synovial Inflammation Quantification Using Computer Vision. ACR Open Rheumatol. 2022 Apr;4(4):322-331. PubMed PMID: 35014221
Fritz D, Inamo J, Zhang F. Single-cell computational machine learning approaches to immune-mediated inflammatory disease: New tools uncover novel fibroblast and macrophage interactions driving pathogenesis. Front Immunol. 2022;13:1076700. PubMed PMID: 36685542
Zhang F, Mears JR, Shakib L, Beynor JI, Shanaj S, Korsunsky I, Nathan A, Donlin LT, Raychaudhuri S. IFN-? and TNF-a drive a CXCL10+ CCL2+ macrophage phenotype expanded in severe COVID-19 lungs and inflammatory diseases with tissue inflammation. Genome Med. 2021 Apr 20;13(1):64. PubMed PMID: 33879239
Mysore V, Cullere X, Mears J, Rosetti F, Okubo K, Liew PX, Zhang F, Madera-Salcedo I, Rosenbauer F, Stone RM, Aster JC, von Andrian UH, Lichtman AH, Raychaudhuri S, Mayadas TN. Fc?R engagement reprograms neutrophils into antigen cross-presenting cells that elicit acquired anti-tumor immunity. Nat Commun. 2021 Aug 9;12(1):4791. PubMed PMID: 34373452
Kang JB, Nathan A, Weinand K, Zhang F, Millard N, Rumker L, Moody DB, Korsunsky I, Raychaudhuri S. Efficient and precise single-cell reference atlas mapping with Symphony. Nat Commun. 2021 Oct 7;12(1):5890. PubMed PMID: 34620862
Orange DE, Yao V, Sawicka K, Fak J, Frank MO, Parveen S, Blachere NE, Hale C, Zhang F, Raychaudhuri S, Troyanskaya OG, Darnell RB. RNA Identification of PRIME Cells Predicting Rheumatoid Arthritis Flares. N Engl J Med. 2020 Jul 16;383(3):218-228. PubMed PMID: 32668112
Kuo D, Ding J, Cohn IS, Zhang F, Wei K, Rao DA, Rozo C, Sokhi UK, Shanaj S, Oliver DJ, Echeverria AP, DiCarlo EF, Brenner MB, Bykerk VP, Goodman SM, Raychaudhuri S, Rätsch G, Ivashkiv LB, Donlin LT. HBEGF(+) macrophages in rheumatoid arthritis induce fibroblast invasiveness. Sci Transl Med. 2019 May 8;11(491). PubMed PMID: 31068444
Zhang F, Wei K, Slowikowski K, Fonseka CY, Rao DA, Kelly S, Goodman SM, Tabechian D, Hughes LB, Salomon-Escoto K, Watts GFM, Jonsson AH, Rangel-Moreno J, Meednu N, Rozo C, Apruzzese W, Eisenhaure TM, Lieb DJ, Boyle DL, Mandelin AM 2nd, Boyce BF, DiCarlo E, Gravallese EM, Gregersen PK, Moreland L, Firestein GS, Hacohen N, Nusbaum C, Lederer JA, Perlman H, Pitzalis C, Filer A, Holers VM, Bykerk VP, Donlin LT, Anolik JH, Brenner MB, Raychaudhuri S. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nat Immunol. 2019 Jul;20(7):928-942. PubMed PMID: 31061532
Korsunsky I, Millard N, Fan J, Slowikowski K, Zhang F, Wei K, Baglaenko Y, Brenner M, Loh PR, Raychaudhuri S. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat Methods. 2019 Dec;16(12):1289-1296. PubMed PMID: 31740819
Arazi A, Rao DA, Berthier CC, Davidson A, Liu Y, Hoover PJ, Chicoine A, Eisenhaure TM, Jonsson AH, Li S, Lieb DJ, Zhang F, Slowikowski K, Browne EP, Noma A, Sutherby D, Steelman S, Smilek DE, Tosta P, Apruzzese W, Massarotti E, Dall'Era M, Park M, Kamen DL, Furie RA, Payan-Schober F, Pendergraft WF 3rd, McInnis EA, Buyon JP, Petri MA, Putterman C, Kalunian KC, Woodle ES, Lederer JA, Hildeman DA, Nusbaum C, Raychaudhuri S, Kretzler M, Anolik JH, Brenner MB, Wofsy D, Hacohen N, Diamond B. Publisher Correction: The immune cell landscape in kidneys of patients with lupus nephritis. Nat Immunol. 2019 Oct;20(10):1404. PubMed PMID: 31409923
Zhang F, Flaherty P. Variational inference for rare variant detection in deep, heterogeneous next-generation sequencing data. BMC Bioinformatics. 2017 Jan 19;18(1):45. PubMed PMID: 28103803
He Y, Zhang F, Flaherty P. RVD2: an ultra-sensitive variant detection model for low-depth heterogeneous next-generation sequencing data. Bioinformatics. 2015 Sep 1;31(17):2785-93. PubMed PMID: 25931517
Zhang, F.*, Jonsson, A.H.*, Nathan, A.*, Wei, K.*, Millard, N.*, et al, Cellular deconstruction of inflamed synovium defines diverse inflammatory phenotypes in rheumatoid arthritis, bioRxiv, In review, 2022
Liu, S.*, Li, L.*, Zhang, F*, …, Church, G., Iterative transcription factor screening enables rapid generation of microglia-like cells from human iPSC, bioRxiv, In review, 2022