The recent advent of CRISPR and other molecular tools enabled the reconstruction of cell lineages based on induced DNA mutations and promises to solve the ones of more complex organisms. To date, no lineage reconstruction algorithms have been rigorously examined for their performance and robustness across dataset types and number of cells. To benchmark such methods, we decided to organize a DREAM challenge using in vitro experimental intMEMOIR recordings and in silico data for a C. elegans lineage tree of about 1,000 cells and a Mus musculus tree of 10,000 cells. Some of the 22 approaches submitted had excellent performance, but structural features of the trees prevented optimal reconstructions. Using smaller sub-trees as training sets proved to be a good approach for tuning algorithms to reconstruct larger trees. The simulation and reconstruction methods here generated delineate a potential way forward for solving larger cell lineage trees such as in mouse.
Bibliographical noteFunding Information:
Funding: the research was funded by the Paul G. Allen Frontiers Group Prime Awarding Agency and HFSP (RGP0002/2016) to I.S.-M. and M.J.T. A.A.G. I.S.-M. O.R. Y.G. Z.L. N.Y. J.S. M.J.T. E.S. M.B.E. and P.M. designed research; A.A.G. O.R. I.S.-M. W.G. J.H. H.Z. R.R. M.G.J. and P.M. analyzed data; K.-H.K.C. I.-Y.K. Al.P. Au.P. A.K. R.Z. S.R. R.W. P.R. V.G.S. N.S. A.R. T.J. R.S. J.P. L.H. and X.S. analyzed data; A.A.G. O.R. I.S. W.G. J.H. H.Z. R.R. M.G.J. and P.M. wrote the manuscript. The authors declare no competing interests. Worm image in Figure 1 was modified from Caenorhabditis elegans hermaphrodite adult-en.svg from Wikimedia Commons by K. D. Schroeder, CC-BY-SA 3.0. The schematic cell lineage of C. elegans in Figures 1 and 6 was generated using the cell lineage web visualization tool CeLaVi available at http://celavi.pro (Salvador-Mart?nez et al. 2020).
Funding: the research was funded by the Paul G. Allen Frontiers Group Prime Awarding Agency and HFSP (RGP0002/2016) to I.S.-M. and M.J.T.
© 2021 The Authors
- C. elegans
- M. musculus
- cell lineage tracing
- lineage reconstruction
- machine learning
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't