Joint Representation and Visualization of Derailed Cell States with Decipher

Overview

Journal bioRxiv

Date 2023 Nov 28

PMID 38014231

Authors

Achille Nazaret

Joy Linyue Fan

Vincent-Philippe Lavallee

Cassandra Burdziak

Andrew E Cornish

Vaidotas Kiseliovas

Robert L Bowman

Ignas Masilionis

Jaeyoung Chun

Shira E Eisman

James Wang

Justin Hong

Lingting Shi

Ross L Levine

Linas Mazutis

David Blei

Dana Peer

Elham Azizi

Affiliations

Soon will be listed here.

Abstract

Biological insights often depend on comparing conditions such as disease and health, yet we lack effective computational tools for integrating single-cell genomics data across conditions or characterizing transitions from normal to deviant cell states. Here, we present Decipher, a deep generative model that characterizes derailed cell-state trajectories. Decipher jointly models and visualizes gene expression and cell state from normal and perturbed single-cell RNA-seq data, revealing shared and disrupted dynamics. We demonstrate its superior performance across diverse contexts, including in pancreatitis with oncogene mutation, acute myeloid leukemia, and gastric cancer.

References

Granja J, Corces M, Pierce S, Bagdatli S, Choudhry H, Chang H . ArchR is a scalable software package for integrative single-cell chromatin accessibility analysis. Nat Genet. 2021; 53(3):403-411. PMC: 8012210. DOI: 10.1038/s41588-021-00790-6. View

Heo S, Noh E, Ju L, Sung J, Jeong Y, Cheon J . CD45CD34CD38CD133 cells have the potential as leukemic stem cells in acute myeloid leukemia. BMC Cancer. 2020; 20(1):285. PMC: 7137473. DOI: 10.1186/s12885-020-06760-1. View

Azizi E, Carr A, Plitas G, Cornish A, Konopacki C, Prabhakaran S . Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment. Cell. 2018; 174(5):1293-1308.e36. PMC: 6348010. DOI: 10.1016/j.cell.2018.05.060. View

Pan X, Chen J, Wang L, Xiao R, Liu L, Fang Z . Inhibition of c-Myc overcomes cytotoxic drug resistance in acute myeloid leukemia cells by promoting differentiation. PLoS One. 2014; 9(8):e105381. PMC: 4134294. DOI: 10.1371/journal.pone.0105381. View

Otto D, Jordan C, Dury B, Dien C, Setty M . Quantifying cell-state densities in single-cell phenotypic landscapes using Mellon. Nat Methods. 2024; 21(7):1185-1195. DOI: 10.1038/s41592-024-02302-w. View

Burdziak C, Alonso-Curbelo D, Walle T, Reyes J, Barriga F, Haviv D . Epigenetic plasticity cooperates with cell-cell interactions to direct pancreatic tumorigenesis. Science. 2023; 380(6645):eadd5327. PMC: 10316746. DOI: 10.1126/science.add5327. View

Abelson S, Collord G, Ng S, Weissbrod O, Mendelson Cohen N, Niemeyer E . Prediction of acute myeloid leukaemia risk in healthy individuals. Nature. 2018; 559(7714):400-404. PMC: 6485381. DOI: 10.1038/s41586-018-0317-6. View

McDowell I, Manandhar D, Vockley C, Schmid A, Reddy T, Engelhardt B . Clustering gene expression time series data using an infinite Gaussian process mixture model. PLoS Comput Biol. 2018; 14(1):e1005896. PMC: 5786324. DOI: 10.1371/journal.pcbi.1005896. View

Muus C, Luecken M, Eraslan G, Sikkema L, Waghray A, Heimberg G . Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics. Nat Med. 2021; 27(3):546-559. PMC: 9469728. DOI: 10.1038/s41591-020-01227-z. View

10.

Street K, Risso D, Fletcher R, Das D, Ngai J, Yosef N . Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics. BMC Genomics. 2018; 19(1):477. PMC: 6007078. DOI: 10.1186/s12864-018-4772-0. View

11.

Sandelin A, Alkema W, Engstrom P, Wasserman W, Lenhard B . JASPAR: an open-access database for eukaryotic transcription factor binding profiles. Nucleic Acids Res. 2003; 32(Database issue):D91-4. PMC: 308747. DOI: 10.1093/nar/gkh012. View

12.

Kanton S, Boyle M, He Z, Santel M, Weigert A, Sanchis-Calleja F . Organoid single-cell genomic atlas uncovers human-specific features of brain development. Nature. 2019; 574(7778):418-422. DOI: 10.1038/s41586-019-1654-9. View

13.

Brunetti L, Gundry M, Sorcini D, Guzman A, Huang Y, Ramabadran R . Mutant NPM1 Maintains the Leukemic State through HOX Expression. Cancer Cell. 2018; 34(3):499-512.e9. PMC: 6159911. DOI: 10.1016/j.ccell.2018.08.005. View

14.

Haghverdi L, Buettner F, Theis F . Diffusion maps for high-dimensional single-cell analysis of differentiation data. Bioinformatics. 2015; 31(18):2989-98. DOI: 10.1093/bioinformatics/btv325. View

15.

Gayoso A, Lopez R, Xing G, Boyeau P, Amiri V, Hong J . A Python library for probabilistic analysis of single-cell omics data. Nat Biotechnol. 2022; 40(2):163-166. DOI: 10.1038/s41587-021-01206-w. View

16.

Yeaton A, Cayanan G, Loghavi S, Dolgalev I, Leddin E, Loo C . The Impact of Inflammation-Induced Tumor Plasticity during Myeloid Transformation. Cancer Discov. 2022; 12(10):2392-2413. PMC: 9547930. DOI: 10.1158/2159-8290.CD-21-1146. View

17.

Bachireddy P, Azizi E, Burdziak C, Nguyen V, Ennis C, Maurer K . Mapping the evolution of T cell states during response and resistance to adoptive cellular therapy. Cell Rep. 2021; 37(6):109992. PMC: 9035342. DOI: 10.1016/j.celrep.2021.109992. View

18.

Corradi G, Bassani B, Simonetti G, Sangaletti S, Vadakekolathu J, Fontana M . Release of IFNγ by Acute Myeloid Leukemia Cells Remodels Bone Marrow Immune Microenvironment by Inducing Regulatory T Cells. Clin Cancer Res. 2022; 28(14):3141-3155. DOI: 10.1158/1078-0432.CCR-21-3594. View

19.

Collins C, Hess J . Role of HOXA9 in leukemia: dysregulation, cofactors and essential targets. Oncogene. 2015; 35(9):1090-8. PMC: 4666810. DOI: 10.1038/onc.2015.174. View

20.

Lotfollahi M, Naghipourfar M, Luecken M, Khajavi M, Buttner M, Wagenstetter M . Mapping single-cell data to reference atlases by transfer learning. Nat Biotechnol. 2021; 40(1):121-130. PMC: 8763644. DOI: 10.1038/s41587-021-01001-7. View