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Klimm, F.

Publications and source records attributed to Klimm, F..

2 recordsLinked to original sources

Hypergraphs for predicting essential genes using multiprotein complex data

Protein-protein interactions are crucial in many biological pathways and facilitate cellular function. Investigating these interactions as a graph of pairwise interactions can help to gain a systemic understanding of cellular processes. It is known, however, that proteins interact with each other not exclusively in pairs but also in polyadic interactions and they can form multiprotein complexes, which are stable interactions between multiple proteins. In this manuscript, we use hypergraphs to investigate multiprotein complex data. We investigate two random null models to test which hypergraph properties occur as a consequence of constraints, such as the size and the number of multiprotein complexes. We find that assortativity, the number of connected components, and clustering differ from the data to these null models. Our main finding is that projecting a hypergraph of polyadic interactions onto a graph of pairwise interactions leads to the identification of different proteins as hubs than the hyper-graph. We find in our data set that the hypergraph degree is a more accurate predictor for gene-essentiality than the degree in the pairwise graph. We find that analysing a hypergraph as pairwise graph drastically changes the distribution of the local clustering coefficient. Furthermore, using a pairwise interaction representing multiprotein complex data may lead to a spurious hierarchical structure, which is not observed in the hypergraph. Hence, we illustrate that hypergraphs can be more suitable than pairwise graphs for the analysis of multiprotein complex data.

systems biology

Functional module detection through integration of single-cell RNA sequencing data with protein-protein interaction networks

Recent advances in single-cell RNA sequencing (scRNA-seq) have allowed researchers to explore transcriptional function at a cellular level. In this study, we present O_SCPLOWSCC_SCPLOWPPIN, a method for integrating single-cell RNA sequencing data with protein-protein interaction networks (PPINs) that detects active modules in cells of different transcriptional states. We achieve this by clustering RNA-sequencing data, identifying differentially expressed genes, constructing node-weighted PPINs, and finding the maximum-weight connected subgraphs with an exact Steiner-tree approach. As a case study, we investigate RNA-sequencing data from human liver spheroids but the techniques described here are applicable to other organisms and tissues. O_SCPLOWSCC_SCPLOWPPIN allows us to expand the output of differential expressed genes analysis with information from protein interactions. We find that different transcriptional states have different subnetworks of the PPIN significantly enriched which represent biological pathways. In these pathways, O_SCPLOWSCC_SCPLOWPPIN also identifies proteins that are not differentially expressed but have a crucial biological function (e.g., as receptors) and therefore reveals biology beyond a standard differentially expressed gene analysis.

bioinformatics