Single-cell regulatory network inference and clustering from high-dimensional sequencing data

Abstract

We are in the big data era which has affected several domains including biomedicine and healthcare. This revolution driven by the explosion of biomedical data offers the potential for better understanding of biology and human diseases. An illustrative example is the emerging single-cell sequencing technologies, which isolate and measure each cell individually, taking a step beyond the traditional techniques where consider their measurements from a bulk of cell. Although big single-cell RNA sequencing (scRNA-seq) data promises valuable insights into the cellular level, their volume poses several challenges related to the ultra-high dimensionality. Furthermore, to further elucidate the potential of these data, more insight into gene regulatory networks (GRN) is required. Network-based approaches can tackle part of the inherent complexity of human diseases, however, the challenges related to the ultra-high dimensionality are increased. Towards this direction, we propose the NIRP, an algorithm that copes with the high dimensionality of scRNA-data using a workflow based on fast multiple random projections and a radius-based nearest neighbors search. NIRP infers a gene regulatory network (GRN) from big scRNA-seq data by transforming the original data space to a lower dimensions space and capturing the similarities among gene expressions. The network is further analyzed using a random walk approach in order to achieve dense subgraphs, active to the case under study. The performance of NIRP is evaluated in a real single-cell experimental study among three well-established GRN tools. Our results make NIRP a reliable tool, able to handle big single-cell data with ultra-high dimensionality and complexity. he main advantage of this method is that it is not affected by the volume, as much as it increases, since it transforms the data space to a specific low dimensional space. © 2019 IEEE.