Browsing by Subject "SIMILARITY"

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  • Ravikumar, Balaguru; Alam, Zaid; Peddinti, Gopal; Aittokallio, Tero (2017)
    The advent of polypharmacology paradigm in drug discovery calls for novel chemoinformatic tools for analyzing compounds' multi-targeting activities. Such tools should provide an intuitive representation of the chemical space through capturing and visualizing underlying patterns of compound similarities linked to their polypharmacological effects. Most of the existing compound-centric chemoinformatics tools lack interactive options and user interfaces that are critical for the real-time needs of chemical biologists carrying out compound screening experiments. Toward that end, we introduce C-SPADE, an open-source exploratory web-tool for interactive analysis and visualization of drug profiling assays (biochemical, cell-based or cell-free) using compound-centric similarity clustering. C-SPADE allows the users to visually map the chemical diversity of a screening panel, explore investigational compounds in terms of their similarity to the screening panel, perform polypharmacological analyses and guide drug-target interaction predictions. C-SPADE requires only the raw drug profiling data as input, and it automatically retrieves the structural information and constructs the compound clusters in real-time, thereby reducing the time required for manual analysis in drug development or repurposing applications. The web-tool provides a customizable visual workspace that can either be downloaded as figure or Newick tree file or shared as a hyperlink with other users. C-SPADE is freely available at
  • Siqueira, Tadeu; Saito, Victor S.; Bini, Luis M.; Melo, Adriano S.; Petsch, Danielle K.; Landeiro, Victor L.; Tolonen, Kimmo T.; Jyrkänkallio-Mikkola, Jenny; Soininen, Janne; Heino, Jani (2020)
    Ecological drift can override the effects of deterministic niche selection on small populations and drive the assembly of some ecological communities. We tested this hypothesis with a unique data set sampled identically in 200 streams in two regions (tropical Brazil and boreal Finland) that differ in macroinvertebrate community size by fivefold. Null models allowed us to estimate the magnitude to which beta-diversity deviates from the expectation under a random assembly process while taking differences in richness and relative abundance into account, i.e., beta-deviation. We found that both abundance- and incidence-based beta-diversity was negatively related to community size only in Brazil. Also, beta-diversity of small tropical communities was closer to stochastic expectations compared with beta-diversity of large communities. We suggest that ecological drift may drive variation in some small communities by changing the expected outcome of niche selection, increasing the chances of species with low abundance and narrow distribution to occur in some communities. Habitat destruction, overexploitation, pollution, and reductions in connectivity have been reducing the size of biological communities. These environmental pressures might make smaller communities more vulnerable to novel conditions and render community dynamics more unpredictable. Incorporation of community size into ecological models should provide conceptual and applied insights into a better understanding of the processes driving biodiversity.
  • Carvalho, Jose C.; Cardoso, Pedro (2020)
    Hutchinson's n-dimensional hypervolume concept holds a central role across different fields of ecology and evolution. The question of the amount of hypervolume overlap and differentiation between species is of great interest to understand the processes that drive niche dynamics, competitive interactions and, ultimately, community assembly. A framework is proposed to decompose overall differentiation among hypervolumes into two distinct components: niche shifts and niche contraction/expansion processes. Niche shift corresponds to the replacement of space between the hypervolumes occupied by two species, whereas niche contraction/expansion processes correspond to net differences between the amount of space enclosed by each hypervolume. A procedure to implement non-continuous trait data in the estimation ofn-dimensional hypervolumes is proposed. Hypervolumes were constructed for three Darwin' finches,Geospiza conirostris,Geospiza magnirostris, andGeospiza difficilisusing intraspecific trait data. Results showed that significant niche shifts, not niche contraction, occurred betweenG. conirostrisandG. magnirostrisin Genovesa island, where they live in sympatry. This means thatG. conirostrisoccupied a different niche space and not a reduced space on Genovesa.G. difficiliswas well differentiated from the other two species. The proposed framework allows disentangling different processes underlying niche partitioning between coexisting species. This framework offers novel insights to understand the drivers of niche partitioning strategies among coexisting species.
  • Vilmi, Annika; Zhao, Wenqian; Picazo, Félix; Li, Mingjia; Heino, Jani; Soininen, Janne; Wang, Jianjun (2020)
    Understanding the role of climatic variation on biodiversity is of chief importance due to the ongoing biodiversity loss and climate change. Freshwaters, one of the most threatened ecosystems in the world, offer a valuable context to study biodiversity patterns of distinct organism groups in relation to climatic variation. In the Tibetan Plateau biodiversity hotspot, we studied the effects of climate and local physico-chemical factors on stream microorganisms (i.e. bacteria) and macroorganisms (i.e. macroinvertebrates) in two parallel catchments with contrasting precipitation and temperature. Diversities and community structures were better explained by climatic and local environmental variables in the drier and colder catchment and at higher elevations, than in the warmer and wetter conditions and at lower elevations. This suggests that communities may be more strongly assembled by deterministic processes in the former, comparatively harsher conditions, compared to the latter, more benign conditions. Macroinvertebrates were more strongly affected by climatic and local environmental factors compared to bacteria, but the diversities and community structures of the two groups showed spatially similar responses to overall abiotic variation, being especially evident with their community structures’ responses to climate. Furthermore, bacterial and macroinvertebrate diversities were positively correlated in the drier and colder catchment, implying that these biologically and ecologically distinct organism groups are likely to be driven by similar processes in areas with such climatic conditions. We conclude that changes in climatic and local environmental conditions may affect the diversity of macroorganisms more strongly than that of microorganisms, at least in subtropical mountainous stream ecosystems studied here, but simultaneous responses of both groups to environmental changes can also be expected.
  • Mammola, Stefano; Cardoso, Pedro (2020)
    The use ofn-dimensional hypervolumes in trait-based ecology is rapidly increasing. By representing the functional space of a species or community as a Hutchinsonian niche, the abstract Euclidean space defined by a set of independent axes corresponding to individuals or species traits, these multidimensional techniques show great potential for the advance of functional ecology theory. In the panorama of existing methods for delineating multidimensional spaces, therpackagehypervolume(Global Ecology and Biogeography, 23, 2014, 595-609) is currently the most used. However, functions for calculating the standard set of functional diversity (FD) indices-richness, divergence and regularity-have not been developed within thehypervolumeframework yet. This gap is delaying its full exploitation in functional ecology, meanwhile preventing the possibility to compare its performance with that of other methods. We develop a set of functions to calculate FD indices based onn-dimensional hypervolumes, including alpha (richness), beta (and respective components), dispersion, evenness, contribution and originality. Altogether, these indices provide a coherent framework to explore the primary mathematical components of FD within a multidimensional setting. These new functions can work either with hypervolume objects or with raw data (species presence or abundance and their traits) as input data, and are versatile in terms of input parameters and options. These functions are implemented withinbat(Biodiversity Assessment Tools), anrpackage for biodiversity assessments. As a coherent corpus of functional indices based on a common algorithm, it opens the possibility to fully explore the strengths of the Hutchinsonian niche concept in community ecology research.
  • Stepanenko, Olesya V.; Stepanenko, Olga V.; Kuznetsova, Irina M.; Shcherbakova, Daria M.; Verkhusha, Vladislav; Turoverov, Konstantin K. (2017)
    Near-infrared (NIR) fluorescent proteins (FPs) designed from PAS (Per-ARNT-Sim repeats) and GAF (cGMP phosphodiesterase/adenylate cyclase/FhlA transcriptional activator) domains of bacterial phytochromes covalently bind biliverdin (BV) chromophore via one or two Cys residues. We studied BV interaction with a series of NIR FP variants derived from the recently reported BphP1-FP protein. The latter was engineered from a bacterial phytochrome RpBphP1, and has two reactive Cys residues (Cys15 in the PAS domain and Cys256 in the GAF domain), whereas its mutants contain single Cys residues either in the PAS domain or in the GAF domain, or no Cys residues. We characterized BphP1-FP and its mutants biochemically and spectroscopically in the absence and in the presence of denaturant. We found that all BphP1-FP variants are monomers. We revealed that spectral properties of the BphP1-FP variants containing either Cys15 or Cys256, or both, are determined by the covalently bound BV chromophore only. Consequently, this suggests an involvement of the inter-monomeric allosteric effects in the BV interaction with monomers in dimeric NIR FPs, such as iRFPs. Likely, insertion of the Cys15 residue, in addition to the Cys256 residue, in dimeric NIR FPs influences BV binding by promoting the BV chromophore covalent cross-linking to both PAS and GAF domains.
  • Dobewall, Henrik; Hintsanen, Mirka; Savelieva, Kateryna; Hakulinen, Christian; Merjonen, Päivi; Gluschkoff, Kia; Keltikangas-Järvinen, Liisa (2019)
    Intergenerational transmission of life satisfaction has been empirically established, but less is known about the continuity of satisfaction as being reflected across multiple life domains, unique effects of parental domain-specific satisfaction on offspring overall life satisfaction, and potential gender effects. In this population-based prospective study, the association between the life satisfaction of parents (G1) (2191 mothers and 2156 fathers) and their children (G2) (921 sons and 1277 daughters) was examined. In both generations, satisfaction as a parent, as a spouse, and at work was assessed in about the same developmental stage (mean age for G1 38-42years, and for G2 38-43years at the times when LS was measured). When both parents were considered jointly, only mothers' overall life satisfaction had an independent effect on their adult children's overall life satisfaction, with the effect diminishing over time. However, we also found a robust effect of paternal satisfaction at work on offspring's overall life satisfaction in adulthood. Gender of the offspring did not significantly moderate the strength of the associations between generations. The current findings emphasize the high interdependence of life satisfaction within families long after children have moved out of the parental home.
  • Morita, Wataru; Morimoto, Naoki; Jernvall, Jukka (2020)
    A major challenge in evolutionary developmental biology is to understand how genetic mutations underlie phenotypic changes. In principle, selective pressures on the phenotype screen the gene pool of the population. Teeth are an excellent model for understanding evolutionary changes in the genotype-phenotype relationship since they exist throughout vertebrates. Genetically modified mice (mutants) with abnormalities in teeth have been used to explore tooth development. The relationship between signaling pathways and molar shape, however, remains elusive due to the high intrinsic complexity of tooth crowns. This hampers our understanding of the extent to which developmental factors explored in mutants explain developmental and phenotypic variation in natural species that represent the consequence of natural selection. Here we combine a novel morphometric method with two kinds of data mining techniques to extract data sets from the three-dimensional surface models of lower first molars: i) machine learning to maximize classification accuracy of 22 mutants, and ii) phylogenetic signal for 31 Murinae species. Major shape variation among mutants is explained by the number of cusps and cusp distribution on a tooth crown. The distribution of mutant mice in morphospace suggests a nonlinear relationship between the signaling pathways and molar shape variation. Comparative analysis of mutants and wild murines reveals that mutant variation overlaps naturally occurring diversity, including more ancestral and derived morphologies. However, taxa with transverse lophs are not fully covered by mutant variation, suggesting experimentally unexplored developmental factors in the evolutionary radiation of Murines. Author summary Teeth are found in almost all vertebrates, and they show many different morphologies. In mammals, especially the cheek teeth or molars are highly diverse in shape, reflecting a vast range of dietary habits and efficiency of occlusion. As teeth are the most durable part of the body, they preserve well in the fossil record. The diversity of molar fossils has been useful in reconstructing the diet and phylogeny of extinct mammals. Genetically modified mice (mutants) show diverse modifications of their molar morphology, but we lack computational tools to test to what extent mutant morphologies account for the natural diversity found in the wild. We developed data mining using machine learning and phylogeny-based methods to analyze three-dimensional molar shapes in mouse mutants and natural species. Although many mutants and species have comparable features, most of the mutant molar variation covers the more evolutionarily ancestral than the more evolutionary derived shapes. Yet to be explored developmental factors may underly the more extreme shapes.
  • He, Siwen; Soininen, Janne; Deng, Guiping; Wang, Beixin (2020)
    A major challenge in community ecology is to understand the underlying factors driving metacommunity (i.e., a set of local communities connected through species dispersal) dynamics. However, little is known about the effects of varying spatial scale on the relative importance of environmental and spatial (i.e., dispersal related) factors in shaping metacommunities and on the relevance of different dispersal pathways. Using a hierarchy of insect metacommunities at three spatial scales (a small, within-stream scale, intermediate, among-stream scale, and large, among-sub-basin scale), we assessed whether the relative importance of environmental and spatial factors shaping metacommunity structure varies predictably across spatial scales, and tested how the importance of different dispersal routes vary across spatial scales. We also studied if different dispersal ability groups differ in the balance between environmental and spatial control. Variation partitioning showed that environmental factors relative to spatial factors were more important for community composition at the within-stream scale. In contrast, spatial factors (i.e., eigenvectors from Moran's eigenvector maps) relative to environmental factors were more important at the among-sub-basin scale. These results indicate that environmental filtering is likely to be more important at the smallest scale with highest connectivity, while dispersal limitation seems to be more important at the largest scale with lowest connectivity. Community variation at the among-stream and among-sub-basin scales were strongly explained by geographical and topographical distances, indicating that overland pathways might be the main dispersal route at the larger scales among more isolated sites. The relative effect of environmental and spatial factors on insect communities varied between low and high dispersal ability groups; this variation was inconsistent among three hierarchical scales. In sum, our study indicates that spatial scale, connectivity, and dispersal ability jointly shape stream metacommunities.
  • Laajala, Teemu D.; Jumppanen, Mikael; Huhtaniemi, Riikka; Fey, Vidal; Kaur, Amanpreet; Knuuttila, Matias; Aho, Eija; Oksala, Riikka; Westermarck, Jukka; Makela, Sari; Poutanen, Matti; Aittokallio, Tero (2016)
    Recent reports have called into question the reproducibility, validity and translatability of the preclinical animal studies due to limitations in their experimental design and statistical analysis. To this end, we implemented a matching-based modelling approach for optimal intervention group allocation, randomization and power calculations, which takes full account of the complex animal characteristics at baseline prior to interventions. In prostate cancer xenograft studies, the method effectively normalized the confounding baseline variability, and resulted in animal allocations which were supported by RNA-seq profiling of the individual tumours. The matching information increased the statistical power to detect true treatment effects at smaller sample sizes in two castration-resistant prostate cancer models, thereby leading to saving of both animal lives and research costs. The novel modelling approach and its open-source and web-based software implementations enable the researchers to conduct adequately-powered and fully-blinded preclinical intervention studies, with the aim to accelerate the discovery of new therapeutic interventions.
  • Ilmarinen, Ville-Juhani; Vainikainen, Mari-Pauliina; Verkasalo, Markku; Lonnqvist, Jan-Erik (2019)
    Sociometric status, the regard that other group members confer to an individual, is one of the most ubiq-uitous and behaviourally relevant attributes assigned to the person by the social environment. Despite this, its contri-bution to personality development has received little attention. The present three-wave longitudinal study, spanningthe age range 7–13 years (n = 1222), sought tofill this gap by examining the transactional pathways between peersociometric status (measured by peer nominations) and Five-Factor personality traits (measured by self-ratingsand parent and teacher ratings). Sociometric status prospectively predicted the development of extraversion. By con-trast, agreeableness and neuroticism prospectively predicted the development of sociometric status. Furthermore,individual-level stability in extraversion was associated with individual-level stability in sociometric status. The re-sults were robust across different sources of personality ratings. We argue that peer sociometric status in the schoolclassroom is the type of environmental effect that has potential to explain personality development. Because of its sta-bility, broadness, and possible impact across a variety of personality processes, sociometric status can both repeti-tiously and simultaneously influence the network of multiple inter-correlated micro-level personality processes,potentially leading to a new network equilibrium that manifests in changes at the level of the broad personality trait.