The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Benchmarking imputation methods for network inference using a novel method of synthetic scRNA-seq data generation
Open accessPublished version of a preprint
Abstract
Background: Single cell RNA-sequencing (scRNA-seq) has very rapidly become the new workhorse of modern biology providing an unprecedented global view on cellular diversity and heterogeneity. In particular, the structure of gene-gene expression correlation contains information on the underlying gene regulatory networks. However, interpretation of scRNA-seq data is challenging due to specific experimental error and biases that are unique to this kind of data including drop-out (or technical zeros). Methods: To deal with this problem several methods for imputation of zeros for scRNA-seq have been developed. However, it is not clear how these processing steps affect inference of genetic networks from single cell data. Here, we introduce Biomodelling.jl, a tool for generation of synthetic scRNA-seq data using multiscale modelling of stochastic gene regulatory networks in growing and dividing cells. Results: Our tool produces realistic transcription data with a known ground truth network topology that can be used to benchmark different approaches for gene regulatory network inference. Using this tool we investigate the impact of different imputation methods on the performance of several network inference algorithms. Conclusions: Biomodelling.jl provides a versatile and useful tool for future development and benchmarking of network inference approaches using scRNA-seq data.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · cited 2×
“Figure 2: Density plots, scatter plots and correlations of 1000 parameter sets sampled from a multivariate normal distribution fitted to experimental data [54].”
BackgroundMethodSplatter: simulation of single-cell RNA sequencing data
Zappia, L., Phipson, B., & Oshlack, A. (2017) · Genome Biology · doi:10.1186/s13059-017-1305-0 · Cited by 905
Single-cell RNA-seq: advances and future challenges
Saliba, A.-E., Westermann, A. J., Gorski, S. A., & Vogel, J. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku555 · Cited by 847
A systematic evaluation of single cell RNA-seq analysis pipelines
Vieth, B., Parekh, S., Ziegenhain, C., Enard, W., & Hellmann, I. (2019) · Nature Communications · doi:10.1038/s41467-019-12266-7 · Cited by 265
Chen, S., & Mar, J. C. (2018) · BMC Bioinformatics · doi:10.1186/s12859-018-2217-z · Cited by 235
Single-cell transcriptomics unveils gene regulatory network plasticity
Iacono, G., Massoni-Badosa, R., & Heyn, H. (2019) · Genome Biology · doi:10.1186/s13059-019-1713-4 · Cited by 218
Jackson, C. A., Castro, D. M., Saldi, G.-A., Bonneau, R., & Gresham, D. (2020) · eLife · doi:10.7554/elife.51254 · Cited by 174
Flagged first, then by citations
Research works printed but not linked: 76
- Davidson E, Levin M. Gene regulatory networks. In:Proceedings of the National Academy of Sciences. 2005;102(14):4935–4935. Publisher: National Academy of Sciences Section: Introduction. · DOI
- Hwang B, Lee JH, Bang D. Single-cell RNA sequencing technologies and bioinformatics pipelines. Exp Mol Med. 2018;50(8):1–14. · DOI
- Lambrechts D, Wauters E, Boeckx B, Aibar S, Nittner D, Burton O, Bassez AD, Pircher A, Van den Eynde K, Weynand B, Verbeken E, Leyn Paul D, Liston A, Vansteenkiste J, Carmeliet P, Aerts S, Thienpont B. Phenotype molding of stromal cells in the lung tumor microenvironment. Nat Med. 2018;24(8):1277–89. · DOI · Paper page
- La Gioele M, Ruslan S, Amit Z, Emelie B, Hannah H, Viktor P, Katja L, Maria EK, Peter L, Alessandro F, Jean F, Lars EB, Zehua L, Van David B, Jimin G, Xiaoling H, Roger B, Erik S, Gonçalo C-B, Patrick C, Igor A, Sten L, Peter VK. RNA velocity of single cells. Nature. 2018;560(7719):494–8. · DOI · Paper page
- Saint M, Bertaux F, Tang W, Sun X-M, Game L, Köferle A, Bähler J, Shahrezaei V, Marguerat S. Single-cell imaging and RNA sequencing reveal patterns of gene expression heterogeneity during fission yeast growth and adaptation. Nat Microbiol. 2019;4(3):480–91. · DOI
- Sara A, Carmen BG-B, Thomas M, Vân Anh H-T, Hana I, Gert H, Florian R, Jean-Christophe M, Pierre G, Jan A, van den Joost O, Zeynep KA, Jasper W, Stein A. SCENIC: single-cell regulatory network inference and clustering. Nat Methods. 2017;14(11):1083–6. · DOI · Paper page
- Chan TE, Stumpf Michael PH, Babtie Ann C. Gene Regulatory Network Inference from Single-Cell Data Using Multivariate Information Measures. Cell Systems. 2017;5(3):251–67. · DOI · Paper page
- Nguyen H, Tran D, Tran B, Pehlivan B, Nguyen T. A comprehensive survey of regulatory network inference methods using single cell rna sequencing data. Brief Bioinf. 2021;22(3):bbaa190. · DOI
- Huang M, Wang J, Torre E, Dueck H, Shaffer S, Bonasio R, Murray John I, Raj A, Li M, Zhang Nancy R. SAVER: gene expression recovery for single-cell RNA sequencing. Nat Methods. 2018;15(7):539–42. · DOI
- Li Wei V, Li Jingyi J. An accurate and robust imputation method scImpute for single-cell RNA-seq data. Nat Commun. 2018;9(1):997. · DOI
- Gong W, Kwak I-Y, Pota P, Koyano-Nakagawa N, Garry Daniel J. DrImpute: imputing dropout events in single cell RNA sequencing data. BMC Bioinf. 2018;19(1):220. · DOI
- Chen Mengjie, Zhou Xiang. VIPER: variability-preserving imputation for accurate gene expression recovery in single-cell RNA sequencing studies. Genome Biol. 2018;19(1):196. · DOI
- van David D, Roshan S, Juozas N, Kristina Y, Pooja K, Ambrose JC, Cassandra B, Kevin RM, Christine LC, Diwakar P, Brian B, Linas M, Guy W, Smita K, Dana P. Recovering gene interactions from single-cell data using data diffusion. Cell. 2018;174(3):716–29. · DOI · Paper page
- Tang W, Bertaux F, Thomas P, Stefanelli C, Saint M, Marguerat S, Shahrezaei V. bayNorm: Bayesian gene expression recovery, imputation and normalization for single-cell RNA-sequencing data. Bioinformatics. 2020;36(4):1174–81. · DOI
- Zhang Lihua, Zhang Shihua. Comparison of computational methods for imputing single-cell RNA-sequencing data. IEEE/ACM Trans Comput Biol Bioinf. 2020;17(2):376–89. · DOI
- Hou Wenpin, Ji Zhicheng, Ji Hongkai, Hicks Stephanie C. A systematic evaluation of single-cell RNA-sequencing imputation methods. Genome Biol. 2020;21(1):218. · DOI
- Lopez R, Regier J, Cole MB, Jordan MI, Yosef N. Deep generative modeling for single-cell transcriptomics. Nat Methods. 2018;15(12):1053–8. · DOI · Paper page
- Eraslan G, Simon Lukas M, Mircea M, Mueller Nikola S, Theis Fabian J. Single-cell RNA-seq denoising using a deep count autoencoder. Nat Commun. 2019;10(1):390. · DOI · Paper page
- Santos-Zavaleta Alberto, Gama-Castro Socorro, Pérez-Rueda Ernesto. A comparative genome analysis of the rpos sigmulon shows a high diversity of responses and origins. Microbiology. 2011;157(5):1393–401. · DOI
- Ly L-H, Vingron M. Effect of imputation on gene network reconstruction from single-cell rna-seq data. bioRxiv. 2021. · DOI
- Camacho Diogo M, Collins James J. Systems biology strikes gold. Cell. 2009;137(1):24–6. · DOI
- Cantone I, Marucci L, Iorio F, Ricci Maria A, Belcastro V, Bansal M, Santini S, Bernardo MD, Bernardo Diego D, Cosma Maria P. A yeast synthetic network for in vivo assessment of reverse-engineering and modeling approaches. Cell. 2009;137(1):172–81. · DOI
- Mendes P, Sha W, Ye K. Artificial gene networks for objective comparison of analysis algorithms. Bioinformatics. 2003;19(suppl 2):ii122–9. · DOI
- Van den Bulcke Tim, Van Leemput Koenraad, Naudts Bart, van Remortel Piet, Ma Hongwu, Verschoren Alain, De Moor Bart, Marchal Kathleen. Syntren: a generator of synthetic gene expression data for design and analysis of structure learning algorithms. BMC Bioinf. 2006;7(1):1–12. · DOI
- Li Yong, Zhu Yanming, Bai Xi, Cai Hua, Ji Wei, Guo Dianjing. Retrn: A retriever of real transcriptional regulatory network and expression data for evaluating structure learning algorithm. Genomics. 2009;94(5):349–54. · DOI
- Hache Hendrik, Lehrach Hans, Herwig Ralf. Reverse engineering of gene regulatory networks: a comparative study. EURASIP J Bioinf Syst Biol. 2009;1–12:2009.
- Payne Samuel H. The utility of protein and mrna correlation. Trends Biochem Sci. 2015;40(1):1–3. · DOI
- Roy S, Werner-Washburne M, Lane T. A system for generating transcription regulatory networks with combinatorial control of transcription. Bioinformatics. 2008;24(10):1318–20. · DOI
- Hache H, Wierling C, Lehrach H, Herwig R. Genge: systematic generation of gene regulatory networks. Bioinformatics. 2009;25(9):1205–7. · DOI
- Haynes Brian C, Brent Michael R. Benchmarking regulatory network reconstruction with grendel. Bioinformatics. 2009;25(6):801–7. · DOI
- Schaffter T, Marbach D, Floreano D. Genenetweaver: in silico benchmark generation and performance profiling of network inference methods. Bioinformatics. 2011;27(16):2263–70. · DOI
- Bellot P, Olsen C, Salembier P, Oliveras-Vergés A, Meyer Patrick E. Netbenchmark: a bioconductor package for reproducible benchmarks of gene regulatory network inference. BMC Bioinf. 2015;16(1):1–15. · DOI
- Marbach D, Costello James C, Küffner R, Vega Nicole M, Prill Robert J, Camacho Diogo M, Allison Kyle R, Kellis M, Collins James J, Stolovitzky G. Wisdom of crowds for robust gene network inference. Nature Methods. 2012;9(8):796–804. · DOI · Paper page
- Greenfield A, Madar A, Ostrer H, Bonneau R. Dream4: combining genetic and dynamic information to identify biological networks and dynamical models. PloS one. 2010;5(10): e13397. · DOI · Paper page
- Milkevych V, Karaman E, Sahana G, Janss L, Cai Z, Lund Mogens S. Mescot: the tool for quantitative trait simulation through the mechanistic modelling of genes’ regulatory interactions. G3 Genes Genomes Genetics. 2021;11:133. · DOI
- Bezanson J, Edelman A, Karpinski S, Shah Viral B. Julia: a fresh approach to numerical computing. SIAM Rev. 2017;59(1):65–98. · DOI · Paper page
- Sun X-M, Bowman A, Priestman M, Bertaux F, Martinez-Segura A, Tang W, Whilding C, Dormann D, Shahrezaei V, Marguerat S. Size-dependent increase in RNA polymerase II initiation rates mediates gene expression scaling with cell size. Curr Biol. 2020;30(7):1217–30. · DOI
- Broido Anna D, Clauset A. Scale-free networks are rare. Nature Commun. 2019;10(1):1017. · DOI · Paper page
- Khanin R, Ernst W. How scale-free are biological networks. J Comput Biol. 2006;13(3):810–8. · DOI
- Zachary OW, Pogacar K, Grotewold E. Topological and statistical analyses of gene regulatory networks reveal unifying yet quantitatively different emergent properties. PLoS Comput Biol. 2018;14:4.
- Espinosa-Soto C. On the role of sparseness in the evolution of modularity in gene regulatory networks. PLOS Comput Biol. 2018;14(5): e1006172. · DOI
- James GM, Sabatti C, Zhou N, Zhu J. Sparse regulatory networks. Ann. Appl Stat. 2010;4(2):663–86.
- Cai X, Bazerque Juan A, Giannakis Georgios B. Inference of gene regulatory networks with sparse structural equation models exploiting genetic perturbations. PLOS Comput Biol. 2013;9(5): e1003068. · DOI
- Gillespie Daniel T. Exact stochastic simulation of coupled chemical reactions. J Phys Chem. 1977;81(25):2340–61. · DOI
- Gillespie Daniel T. The chemical Langevin equation. J Chem Phy. 2000;113(1):297–306. · DOI
- Gillespie Daniel T. Approximate accelerated stochastic simulation of chemically reacting systems. J Chem Phys. 2001;115(4):1716–33. · DOI
- Kempe H, Schwabe A, Crémazy F, Verschure Pernette J, Bruggeman Frank J. The volumes and transcript counts of single cells reveal concentration homeostasis and capture biological noise. Mol Biol Cell. 2015;26(4):797–804. · DOI
- Couturier Charles P, Ayyadhury S, Le Phuong U, Nadaf J, Monlong J, Riva G, Allache R, Baig S, Yan X, Bourgey M, et al. Single-cell rna-seq reveals that glioblastoma recapitulates a normal neurodevelopmental hierarchy. Nat Commun. 2020;11(1):1–19. · DOI · Paper page
- Svensson V, Vento-Tormo R, Teichmann Sarah A. Exponential scaling of single-cell rna-seq in the past decade. Nat Protoc. 2018;13(4):599–604. · DOI · Paper page
- Barabasi N, Albert N. Emergence of scaling in random networks. Science. 1999;286(5439):509–12. · DOI · Paper page
- Tanouchi Y, Pai A, Park H, Huang S, Stamatov R, Buchler NE, You L. A noisy linear map underlies oscillations in cell size and gene expression in bacteria. Nature. 2015;523(7560):357–60. · DOI
- Bertaux François, Marguerat Samuel, Shahrezaei Vahid. Division rate, cell size and proteome allocation: impact on gene expression noise and implications for the dynamics of genetic circuits. Royal Soc Open Sci. 2018;5(3): 172234. · DOI
- Cadart C, Monnier S, Grilli J, Sáez Pablo J, Srivastava N, Attia R, Terriac E, Baum B, Cosentino-Lagomarsino M, Piel M. Size control in mammalian cells involves modulation of both growth rate and cell cycle duration. Nat Commun. 2018;9(1):1–15. · DOI
- Charlebois Daniel A, Balázsi G. Modeling cell population dynamics. In Silico Biol. 2019;13(1–2):21–39. · DOI
- Mora T, Walczak AM. Effect of phenotypic selection on stochastic gene expression. J Phys Chem. 2013;117(42):13194–205. · DOI
- Lee Kangtaek, Matsoukas Themis. Simultaneous coagulation and break-up using constant-n monte carlo. Powder Technol. 2000;110(1):82–9. · DOI
- Mantzaris Nikos V. Stochastic and deterministic simulations of heterogeneous cell population dynamics. J Theor Biol. 2006;241(3):690–706. · DOI
- Thomas Philipp. Intrinsic and extrinsic noise of gene expression in lineage trees. Sci Rep. 2019;9(1):474. · DOI
- Klein AM, Mazutis L, Akartuna I, Tallapragada N, Veres A, Li V, Peshkin L, Weitz DA, Kirschner MW. Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell. 2015;161(5):1187–201. · DOI · Paper page
- Yamawaki TM, Lu DR, Ellwanger Daniel C, Bhatt D, Manzanill P, Arias V, Zhou H, Yoon OhK, Homann O, Wang S, Li C-M. Systematic comparison of high-throughput single-cell RNA-seq methods for immune cell profiling. BMC Genomics. 2021;22(1):66. · DOI
- Vallejos Catalina A, Risso D, Scialdone A, Dudoit S, Marioni John C. Normalizing single-cell RNA sequencing data: challenges and opportunities. Nat Methods. 2017;14(6):565–71. · DOI · Paper page
- Breda J, Zavolan M, van Nimwegen E. Bayesian inference of gene expression states from single-cell RNA-seq data. Nat Biotechnol. 2021;39(8):1008–16. · DOI
- Patruno L, Maspero D, Craighero F, Angaroni F, Antoniotti M, Graudenzi A. A review of computational strategies for denoising and imputation of single-cell transcriptomic data. Brief Bioinf. 2021;22(4):222.
- Chan Thalia E, Pallaseni Ananth V, Babtie Ann C, McEwen Kirsten R, Stumpf Michael PH. Empirical bayes meets information theoretical network reconstruction from single cell data. BioRxiv, 2018;pp. 264853. · DOI
- Huynh-Thu V, Irrthum A, Wehenkel L, Geurts P. Inferring regulatory networks from expression data using tree-based methods. PLOS ONE. 2010;5(9): e12776. · DOI · Paper page
- Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982;143(1):29–36. · DOI · Paper page
- Boyd K, Eng Kevin H, David C. Page. area under the precision-recall curve: point estimates and confidence intervals. In: Hendrik B, Kristian K, Siegfried N, Filip V, editors. Machine learning and knowledge discovery in databases lecture notes in computer science. Berlin: Springer; 2013. p. 451–66.
- Haibo He. Imbalanced Learning: Foundations, Algorithms, and Applications, Wiley.
- Chan Thalia E, Stumpf Michael PH, Babtie Ann C. Gene regulatory network inference from single-cell data using multivariate information measures. Cell Syst. 2017;5(3):251–67. · DOI · Paper page
- Yamawaki Tracy M, Lu Daniel R, Ellwanger Daniel C, Bhatt D, Manzanillo P, Arias V, Zhou H, Yoon OhK, Homann O, Wang S, et al. Systematic comparison of high-throughput single-cell rna-seq methods for immune cell profiling. BMC Genomics. 2021;22(1):1–18.
- Barron M, Li J. Identifying and removing the cell-cycle effect from single-cell rna-sequencing data. Sci Rep. 2016;6(1):1–10. · DOI
- Liu J, Yang M, Zhao W and Xiaobo Z. Ccpe: Cell cycle pseudotime estimation for single cell rna-seq data. bioRxiv; 2021. · DOI
- Hsiao Chiaowen J, Tung P, Blischak John D, Burnett Jonathan E, Barr Kenneth A, Dey Kushal K, Stephens M, Gilad Y. Characterizing and inferring quantitative cell cycle phase in single-cell rna-seq data analysis. Genome Res. 2020;30(4):611–21. · DOI
- Ly L-H, Vingron M. Effect of imputation on gene network reconstruction from single-cell RNA-seq data. bioRxiv, pp. 439623, 2021. · DOI
- Steinheuer Lisa M, Canzler S, Hackermüller J. Benchmarking scRNA-seq imputation tools with respect to network inference highlights deficits in performance at high levels of sparsity. bioRxiv, pp. 438193, 2021. · DOI
- Marouf M, Machart P, Bansal V, Kilian C, Magruder Daniel S, Krebs Christian F, Bonn S. Realistic in silico generation and augmentation of single-cell rna-seq data using generative adversarial networks. Nat Commun. 2020;11(1):1–12. · DOI
Metadata
- Authors
- Lasri, A., Shahrezaei, V., & Sturrock, M.
- Affiliations
- Royal College of Surgeons in Ireland (IE)
- Imperial College London (GB)
- Corresponding author
- Sturrock, Marc
- Venue
- BMC Bioinformatics
- Published
- 2022-06-17
- Volume
- 23
- Issue
- 1
- Pages
- 236-236
- ISSN
- 1471-2105 (ISSN-L)
- PMC
- PMC9204969
- OpenAlex
- W4283009707
- Cited by
- 5
- References
- 7
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2022: 1
- FWCI
- 0.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Bioinformatics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- Funders
- Horizon 2020 Framework Programme (766069)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- single-cell RNA sequencing, gene regulatory network inference, zero imputation, dropout, synthetic data generation, benchmarking, multiscale modeling, gene expression correlation
- MeSH terms
- Software, Sequence Analysis, RNA, Benchmarking, Gene Expression Profiling, Gene Regulatory Networks, Single-Cell Analysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review