A literature-derived knowledge graph augments the interpretation of single cell RNA-seq datasets

March 26,2021

 

April 4, 2021

Abstract: Technology to generate single cell RNA-sequencing (scRNA-seq) datasets and tools to annotate them have rapidly advanced in the past several years. Such tools generally rely on existing transcriptomic datasets or curated databases of cell type defining genes, while the application of scalable natural language processing (NLP) methods to enhance analysis workflows has not been adequately explored. Here we deployed an NLP framework to objectively quantify associations between a comprehensive set of over 20,000 human protein-coding genes and over 500 cell type terms across over 26 million biomedical documents. The resultant gene-cell type associations (GCAs) are significantly stronger between a curated set of matched cell type-marker pairs than the complementary set of mismatched pairs (Mann Whitney p < 6.15x10-76, r = 0.24; Cohens D = 2.6). Building on this, we developed an augmented annotation algorithm that leverages GCAs to categorize cell clusters identified in scRNA-seq datasets, and we tested its ability to predict the cellular identity of 185 clusters in 13 datasets from human blood, pancreas, lung, liver, kidney, retina, and placenta. With the optimized settings, the true cellular identity matched the top prediction in 66% of tested clusters and was present among the top five predictions for 94% of clusters. Further, contextualization of differential expression analyses with these GCAs highlights poorly characterized markers of established cell types, such as CLIC6 and DNASE1L3 in retinal pigment epithelial cells and endothelial cells, respectively. Taken together, this study illustrates for the first time how the systematic application of a literature derived knowledge graph can expedite and enhance the annotation and interpretation of scRNA-seq data.

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Authors:

Deeksha Doddahonnaiah*1Patrick Lenehan*1Travis Hughes1, David Zemmour1Enrique Garcia-Rivera1AJ Venkatakrishnan1, Ramakrisha Chilaka2Apoorv Khare2Akash Anand2, Rakesh Barve2, Viswanathan Thiagarajan2, Venky Soundararajan1
 
1nference, Cambridge, MA 02142, USA
2nference Labs, Bengaluru, KA 560017, India
*Contributed equally
 
Correspondence: Venky Soundararajan (venky@nference.net)
 

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.