Community detection in directed acyclic graphs

Some temporal networks, most notably citation networks, are naturally represented as directed acyclic graphs (DAGs). To detect communities in DAGs, we propose a modularity for DAGs by defining an appropriate null model (i.e., randomized network) respecting the order of nodes. We implement a spectral method to approximately maximize the proposed modularity measure and test the method on citation networks and other DAGs. We find that the attained values of the modularity for DAGs are similar for partitions that we obtain by maximizing the proposed modularity (designed for DAGs), the modularity for undirected networks and that for general directed networks. In other words, if we neglect the order imposed on nodes (and the direction of links) in a given DAG and maximize the conventional modularity measure, the obtained partition is close to the optimal one in the sense of the modularity for DAGs.Comment: 2 figures, 7 table

Steady state and mean recurrence time for random walks on stochastic temporal networks

Random walks are basic diffusion processes on networks and have applications in, for example, searching, navigation, ranking, and community detection. Recent recognition of the importance of temporal aspects on networks spurred studies of random walks on temporal networks. Here we theoretically study two types of event-driven random walks on a stochastic temporal network model that produces arbitrary distributions of interevent-times. In the so-called active random walk, the interevent-time is reinitialized on all links upon each movement of the walker. In the so-called passive random walk, the interevent-time is only reinitialized on the link that has been used last time, and it is a type of correlated random walk. We find that the steady state is always the uniform density for the passive random walk. In contrast, for the active random walk, it increases or decreases with the node's degree depending on the distribution of interevent-times. The mean recurrence time of a node is inversely proportional to the degree for both active and passive random walks. Furthermore, the mean recurrence time does or does not depend on the distribution of interevent-times for the active and passive random walks, respectively.Comment: 5 figure

Temporal interactions facilitate endemicity in the susceptible-infected-susceptible epidemic model

Data of physical contacts and face-to-face communications suggest temporally varying networks as the media on which infections take place among humans and animals. Epidemic processes on temporal networks are complicated by complexity of both network structure and temporal dimensions. Theoretical approaches are much needed for identifying key factors that affect dynamics of epidemics. In particular, what factors make some temporal networks stronger media of infection than other temporal networks is under debate. We develop a theory to understand the susceptible-infected-susceptible epidemic model on arbitrary temporal networks, where each contact is used for a finite duration. We show that temporality of networks lessens the epidemic threshold such that infections persist more easily in temporal networks than in their static counterparts. We further show that the Lie commutator bracket of the adjacency matrices at different times is a key determinant of the epidemic threshold in temporal networks. The effect of temporality on the epidemic threshold, which depends on a data set, is approximately predicted by the magnitude of a commutator norm.Comment: 8 figures, 1 tabl

Balancing selection on genomic deletion polymorphisms in humans

A key question in biology is why genomic variation persists in a population for extended periods. Recent studies have identified examples of genomic deletions that have remained polymorphic in the human lineage for hundreds of millennia, ostensibly owing to balancing selection. Nevertheless, genome-wide investigation of ancient and possibly adaptive deletions remains imperative. Here, we demonstrate an excess of polymorphisms in present-day humans that predate the modern human-Neanderthal split (ancient polymorphisms), which cannot be explained solely by selectively neutral scenarios. We analyze the adaptive mechanisms that underlie this excess in deletion polymorphisms. Using a previously published measure of balancing selection, we show that this excess of ancient deletions is largely owing to balancing selection. Based on the absence of signatures of overdominance, we conclude that it is a rare mode of balancing selection among ancient deletions. Instead, more complex scenarios involving spatially and temporally variable selective pressures are likely more common mechanisms. Our results suggest that balancing selection resulted in ancient deletions harboring disproportionately more exonic variants with GWAS associations. We further found that ancient deletions are significantly enriched for traits related to metabolism and immunity. As a by-product of our analysis, we show that deletions are, on average, more deleterious than single-nucleotide variants. We can now argue that not only is a vast majority of common variants shared among human populations, but a considerable portion of biologically relevant variants has been segregating among our ancestors for hundreds of thousands, if not millions, of years

Fotografía DE DOS JÓVENES EN TONO SONRIENTE [Material gráfico]

Copia digital. Madrid : Ministerio de Educación, Cultura y Deporte, 201

Integrative GWAS and co-localisation analysis suggests novel genes associated with age-related multimorbidity

Abstract Advancing age is the greatest risk factor for developing multiple age-related diseases. Therapeutic approaches targeting the underlying pathways of ageing, rather than individual diseases, may be an effective way to treat and prevent age-related morbidity while reducing the burden of polypharmacy. We harness the Open Targets Genetics Portal to perform a systematic analysis of nearly 1,400 genome-wide association studies (GWAS) mapped to 34 age-related diseases and traits, identifying genetic signals that are shared between two or more of these traits. Using locus-to-gene (L2G) mapping, we identify 995 targets with shared genetic links to age-related diseases and traits, which are enriched in mechanisms of ageing and include known ageing and longevity-related genes. Of these 995 genes, 128 are the target of an approved or investigational drug, 526 have experimental evidence of binding pockets or are predicted to be tractable, and 341 have no existing tractability evidence, representing underexplored genes which may reveal novel biological insights and therapeutic opportunities. We present these candidate targets for exploration and prioritisation in a web application

Grey wolf genomic history reveals a dual ancestry of dogs

The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canisfamiliaris) lived(1-8). Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT8840,000-30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located.Peer reviewe

Epidemic Threshold in Temporally-Switching Networks

Masuda N., Holme P. (eds).Infectious diseases have been modelled on networks that summarise physical contacts or close proximity of individuals. These networks are known to be complex in both their structure and how they change over time. We present an overview of recent progress in numerically determining the epidemic threshold in temporally-switching networks, and illustrate that slower switching of snapshots relative to epidemic dynamics lowers the epidemic threshold. Therefore, ignoring the temporally-varying nature of networks may underestimate endemicity. We also identify a predictor for the magnitude of this shift which is based on the commutator norm of snapshot adjacency matrices.LS acknowledges the support provided through the Engineering and Physical Sciences Research Council (EPSRC) [grant number EP/G03706X/1]. LS and NM acknowledge the support provided through JST, ERATO, Kawarabayashi Large Graph Project. KK acknowledges funding from the Ramón y Cajal program of MINECO. KK and VME acknowledge support from projects SPASIMM (FIS2016-80067-P AEI/FEDER, UE) and NOMAQ (FIS2014-60343-P). NM acknowledges the support provided through JST, CREST.Peer reviewe

Disentangling selection on genetically correlated polygenic traits via whole-genome genealogies.

We present a full-likelihood method to infer polygenic adaptation from DNA sequence variation and GWAS summary statistics to quantify recent transient directional selection acting on a complex trait. Through simulations of polygenic trait architecture evolution and GWASs, we show the method substantially improves power over current methods. We examine the robustness of the method under stratification, uncertainty and bias in marginal effects, uncertainty in the causal SNPs, allelic heterogeneity, negative selection, and low GWAS sample size. The method can quantify selection acting on correlated traits, controlling for pleiotropy even among traits with strong genetic correlation (|rg|=80%) while retaining high power to attribute selection to the causal trait. When the causal trait is excluded from analysis, selection is attributed to its closest proxy. We discuss limitations of the method, cautioning against strongly causal interpretations of the results, and the possibility of undetectable gene-by-environment (GxE) interactions. We apply the method to 56 human polygenic traits, revealing signals of directional selection on pigmentation, life history, glycated hemoglobin (HbA1c), and other traits. We also conduct joint testing of 137 pairs of genetically correlated traits, revealing widespread correlated response acting on these traits (2.6-fold enrichment, p = 1.5 × 10-7). Signs of selection on some traits previously reported as adaptive (e.g., educational attainment and hair color) are largely attributable to correlated response (p = 2.9 × 10-6 and 1.7 × 10-4, respectively). Lastly, our joint test shows antagonistic selection has increased type 2 diabetes risk and decrease HbA1c (p = 1.5 × 10-5)