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Nested Stochastic Block Models applied to the analysis of single cell data.

ABSTRACT: Single cell profiling has been proven to be a powerful tool in molecular biology to understand the complex behaviours of heterogeneous system. The definition of the properties of single cells is the primary endpoint of such analysis, cells are typically clustered to underpin the common determinants that can be used to describe functional properties of the cell mixture under investigation. Several approaches have been proposed to identify cell clusters; while this is matter of active research, one popular approach is based on community detection in neighbourhood graphs by optimisation of modularity. In this paper we propose an alternative and principled solution to this problem, based on Stochastic Block Models. We show that such approach not only is suitable for identification of cell groups, it also provides a solid framework to perform other relevant tasks in single cell analysis, such as label transfer. To encourage the use of Stochastic Block Models, we developed a python library, schist, that is compatible with the popular scanpy framework.

SUBMITTER: Morelli L

PROVIDER: S-EPMC8630903 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Nested Stochastic Block Models applied to the analysis of single cell data.

Morelli Leonardo L Giansanti Valentina V Cittaro Davide D

BMC bioinformatics 20211130 1

Single cell profiling has been proven to be a powerful tool in molecular biology to understand the complex behaviours of heterogeneous system. The definition of the properties of single cells is the primary endpoint of such analysis, cells are typically clustered to underpin the common determinants that can be used to describe functional properties of the cell mixture under investigation. Several approaches have been proposed to identify cell clusters; while this is matter of active research, on ...[more]

PMID: 34847879

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Project description:Background: Biological entities such as genes, promoters, mRNA, metabolites or proteins do not act alone, but in concert in their network context. Modules, i.e., groups of nodes with similar topological properties in these networks characterize important biological functions of the underlying biomolecular system. Edges in such molecular networks represent regulatory and physical interactions, and comparing them between conditions provides valuable information on differential molecular mechanisms. However, biological data is inherently noisy and network reduction techniques can propagate errors particularly to the level of edges. We aim to improve the analysis of networks of biological molecules by deriving modules together with edge relevance estimations that are based on global network characteristics. Methods: The key challenge we address here is investigating the capability of stochastic block models (SBMs) for representing and analyzing different types of biomolecular networks. Fitting them to SBMs both delivers modules of the networks and enables the derivation of edge confidence scores, and it has not yet been investigated for analyzing biomolecular networks. We apply SBM-based analysis independently to three correlation-based networks of breast cancer data originating from high-throughput measurements of different molecular layers: either transcriptomics, proteomics, or metabolomics. The networks were reduced by thresholding for correlation significance or by requirements on scale-freeness. Results and discussion: We find that the networks are best represented by the hierarchical version of the SBM, and many of the predicted blocks have a biologically and phenotypically relevant functional annotation. The edge confidence scores are overall in concordance with the biological evidence given by the measurements. We conclude that biomolecular networks can be appropriately represented and analyzed by fitting SBMs. As the SBM-derived edge confidence scores are based on global network connectivity characteristics and potential hierarchies within the biomolecular networks are considered, they could be used as additional, integrated features in network-based data comparisons.

Project description:Multimodal fusion is becoming more common as it proves to be a powerful approach to identify complementary information from multimodal datasets. However, simulation of joint information is not straightforward. Published approaches mostly employ limited, provisional designs that often break the link between the model assumptions and the data for the sake of demonstrating properties of fusion techniques. This work introduces a new approach to synthetic data generation which allows full-compliance between data and model while still representing realistic spatiotemporal features in accordance with the current neuroimaging literature. The focus is on the simulation of joint information for the verification of stochastic linear models, particularly those used in multimodal data fusion of brain imaging data. Our first goal is to obtain a benchmark ground-truth in which estimation errors due to model mismatch are minimal or none. Then we move on to assess how estimation is affected by gradually increasing model discrepancies toward a more realistic dataset. The key aspect of our approach is that it permits complete control over the type and level of model mismatch, allowing for more educated inferences about the limitations and caveats of select stochastic linear models. As a result, impartial comparison of models is possible based on their performance in multiple different scenarios. Our proposed method uses the commonly overlooked theory of copulas to enable full control of the type and level of dependence/association between modalities, with no occurrence of spurious multimodal associations. Moreover, our approach allows for arbitrary single-modality marginal distributions for any fixed choice of dependence/association between multimodal features. Using our simulation framework, we can rigorously challenge the assumptions of several existing multimodal fusion approaches. Our study brings a new perspective to the problem of simulating multimodal data that can be used for ground-truth verification of various stochastic multimodal models available in the literature, and reveals some important aspects that are not captured or are overlooked by ad hoc simulations that lack a firm statistical motivation.

Dataset Information

Nested Stochastic Block Models applied to the analysis of single cell data.

Publications

Nested Stochastic Block Models applied to the analysis of single cell data.

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