RT Journal Article
SR Electronic
T1 Biological Cartography: Building and Benchmarking Representations of Life
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.12.09.519400
DO 10.1101/2022.12.09.519400
A1 Safiye Celik
A1 Jan-Christian Hütter
A1 Sandra Melo Carlos
A1 Nathan H Lazar
A1 Rahul Mohan
A1 Conor Tillinghast
A1 Tommaso Biancalani
A1 Marta Fay
A1 Berton A Earnshaw
A1 Imran S Haque
YR 2022
UL http://biorxiv.org/content/early/2022/12/12/2022.12.09.519400.abstract
AB The continued scaling of genetic perturbation technologies combined with high-dimensional assays (microscopy and RNA-sequencing) has enabled genome-scale reverse-genetics experiments that go beyond single-endpoint measurements of growth or lethality. Datasets emerging from these experiments can be combined to construct “maps of biology”, in which perturbation readouts are placed in unified, relatable embedding spaces to capture known biological relationships and discover new ones. Construction of maps involves many technical choices in both experimental and computational protocols, motivating the design of benchmark procedures by which to evaluate map quality in a systematic, unbiased manner.In this work, we propose a framework for the steps involved in map building and demonstrate key classes of benchmarks to assess the quality of a map. We describe univariate benchmarks assessing perturbation quality and multivariate benchmarks assessing recovery of known biological relationships from large-scale public data sources. We demonstrate the application and interpretation of these benchmarks through example maps of scRNA-seq and phenomic imaging data.Competing Interest StatementThe authors have declared no competing interest.