Zhana Kuncheva

The circulating proteome offers insights into the biological pathways that underlie disease. Here, we test relationships between 1,468 Olink protein levels and the incidence of 23 age-related diseases and mortality in the UK Biobank (n = 47,600). We report 3,209 associations between 963 protein levels and 21 incident outcomes. Next, protein-based scores (ProteinScores) are developed using penalized Cox regression. When applied to test sets, six ProteinScores improve the area under the curve estimates for the 10-year onset of incident outcomes beyond age, sex and a comprehensive set of 24 lifestyle factors, clinically relevant biomarkers and physical measures. Furthermore, the ProteinScore for type 2 diabetes outperforms a polygenic risk score and HbA1c-a clinical marker used to monitor and diagnose type 2 diabetes. The performance of scores using metabolomic and proteomic features is also compared. These data characterize early proteomic contributions to major age-related diseases, demonstrating the value of the plasma proteome for risk stratification.

Multiplex networks, a special type of multilayer networks, are increasingly applied in many domains ranging from social media analytics to biology. A common task in these applications concerns the detection of community structures. Many existing algorithms for community detection in multiplexes attempt to detect communities which are shared by all layers. In this article we propose a community detection algorithm, LART (Locally Adaptive Random Transitions), for the detection of communities that are shared by either some or all the layers in the multiplex. The algorithm is based on a random walk on the multiplex, and the transition probabilities defining the random walk are allowed to depend on the local topological similarity between layers at any given node so as to facilitate the exploration of communities across layers. Based on this random walk, a node dissimilarity measure is derived and nodes are clustered based on this distance in a hierarchical fashion. We present experimental results using networks simulated under various scenarios to showcase the performance of LART in comparison to related community detection algorithms.

Microbes in the gut microbiome form sub-communities based on shared niche specialisations and specific interactions between individual taxa. The inter-microbial relationships that define these communities can be inferred from the co-occurrence of taxa across multiple samples. Here, we present an approach to identify comparable communities within different gut microbiota co-occurrence networks, and demonstrate its use by comparing the gut microbiota community structures of three geographically diverse populations. We combine gut microbiota profiles from 2,764 British, 1,023 Dutch, and 639 Israeli individuals, derive co-occurrence networks between their operational taxonomic units, and detect comparable communities within them. Comparing populations we find that community structure is significantly more similar between datasets than expected by chance. Mapping communities across the datasets, we also show that communities can have similar associations to host phenotypes in different populations. This study shows that the community structure within the gut microbiota is stable across populations, and describes a novel approach that facilitates comparative community-centric microbiome analyses.

Abstract The circulating proteome offers insights into the biological pathways that underlie disease. Here, we test relationships between 1,468 Olink protein levels and the incidence of 23 age-related diseases and mortality, over 16 years of electronic health linkage in the UK Biobank (N=47,600). We report 3,201 associations between 961 protein levels and 21 incident outcomes, identifying proteomic indicators of multiple morbidities. Next, protein-based scores (ProteinScores) are developed using penalised Cox regression. When applied to test sets, six ProteinScores improve Area Under the Curve (AUC) estimates for the 10-year onset of incident outcomes beyond age, sex and a comprehensive set of 24 lifestyle factors, clinically-relevant biomarkers and physical measures. Furthermore, the ProteinScore for type 2 diabetes outperformed a polygenic risk score, a metabolomic score and HbA1c – a clinical marker used to monitor and diagnose type 2 diabetes. These data characterise early proteomic contributions to major age-related disease and demonstrate the value of the plasma proteome for risk stratification.

Multiplex networks, a special type of multilayer networks, are increasingly applied in many domains ranging from social media analytics to biology. A common task in these applications concerns the detection of community structures. Many existing algorithms for community detection in multiplexes attempt to detect communities which are shared by all layers. In this article we propose a community detection algorithm, LART (Locally Adaptive Random Transitions), for the detection of communities that are shared by either some or all the layers in the multiplex. The algorithm is based on a random walk on the multiplex, and the transition probabilities defining the random walk are allowed to depend on the local topological similarity between layers at any given node so as to facilitate the exploration of communities across layers. Based on this random walk, a node dissimilarity measure is derived and nodes are clustered based on this distance in a hierarchical fashion. We present experimental results using networks simulated under various scenarios to showcase the performance of LART in comparison to related community detection algorithms.