5,379 research outputs found
Spherical harmonics coeffcients for ligand-based virtual screening of cyclooxygenase inhibitors
Background: Molecular descriptors are essential for many applications in computational chemistry, such as ligand-based similarity searching. Spherical harmonics have previously been suggested as comprehensive descriptors of molecular structure and properties. We investigate a spherical harmonics descriptor for shape-based virtual screening. Methodology/Principal Findings: We introduce and validate a partially rotation-invariant three-dimensional molecular shape descriptor based on the norm of spherical harmonics expansion coefficients. Using this molecular representation, we parameterize molecular surfaces, i.e., isosurfaces of spatial molecular property distributions. We validate the shape descriptor in a comprehensive retrospective virtual screening experiment. In a prospective study, we virtually screen a large compound library for cyclooxygenase inhibitors, using a self-organizing map as a pre-filter and the shape descriptor for candidate prioritization. Conclusions/Significance: 12 compounds were tested in vitro for direct enzyme inhibition and in a whole blood assay. Active compounds containing a triazole scaffold were identified as direct cyclooxygenase-1 inhibitors. This outcome corroborates the usefulness of spherical harmonics for representation of molecular shape in virtual screening of large compound collections. The combination of pharmacophore and shape-based filtering of screening candidates proved to be a straightforward approach to finding novel bioactive chemotypes with minimal experimental effort
A network model of interpersonal alignment in dialog
In dyadic communication, both interlocutors adapt to each other linguistically, that is, they align interpersonally. In this article, we develop a framework for modeling interpersonal alignment in terms of the structural similarity of the interlocutorsâ dialog lexica. This is done by means of so-called two-layer time-aligned network series, that is, a time-adjusted graph model. The graph model is partitioned into two layers, so that the interlocutorsâ lexica are captured as subgraphs of an encompassing dialog graph. Each constituent network of the series is updated utterance-wise. Thus, both the inherent bipartition of dyadic conversations and their gradual development are modeled. The notion of alignment is then operationalized within a quantitative model of structure formation based on the mutual information of the subgraphs that represent the interlocutorâs dialog lexica. By adapting and further developing several models of complex network theory, we show that dialog lexica evolve as a novel class of graphs that have not been considered before in the area of complex (linguistic) networks. Additionally, we show that our framework allows for classifying dialogs according to their alignment status. To the best of our knowledge, this is the first approach to measuring alignment in communication that explores the similarities of graph-like cognitive representations. Keywords: alignment in communication; structural coupling; linguistic networks; graph distance measures; mutual information of graphs; quantitative network analysi
Metrics for Graph Comparison: A Practitioner's Guide
Comparison of graph structure is a ubiquitous task in data analysis and
machine learning, with diverse applications in fields such as neuroscience,
cyber security, social network analysis, and bioinformatics, among others.
Discovery and comparison of structures such as modular communities, rich clubs,
hubs, and trees in data in these fields yields insight into the generative
mechanisms and functional properties of the graph.
Often, two graphs are compared via a pairwise distance measure, with a small
distance indicating structural similarity and vice versa. Common choices
include spectral distances (also known as distances) and distances
based on node affinities. However, there has of yet been no comparative study
of the efficacy of these distance measures in discerning between common graph
topologies and different structural scales.
In this work, we compare commonly used graph metrics and distance measures,
and demonstrate their ability to discern between common topological features
found in both random graph models and empirical datasets. We put forward a
multi-scale picture of graph structure, in which the effect of global and local
structure upon the distance measures is considered. We make recommendations on
the applicability of different distance measures to empirical graph data
problem based on this multi-scale view. Finally, we introduce the Python
library NetComp which implements the graph distances used in this work
Revisiting Date and Party Hubs: Novel Approaches to Role Assignment in Protein Interaction Networks
The idea of 'date' and 'party' hubs has been influential in the study of
protein-protein interaction networks. Date hubs display low co-expression with
their partners, whilst party hubs have high co-expression. It was proposed that
party hubs are local coordinators whereas date hubs are global connectors. Here
we show that the reported importance of date hubs to network connectivity can
in fact be attributed to a tiny subset of them. Crucially, these few, extremely
central, hubs do not display particularly low expression correlation,
undermining the idea of a link between this quantity and hub function. The
date/party distinction was originally motivated by an approximately bimodal
distribution of hub co-expression; we show that this feature is not always
robust to methodological changes. Additionally, topological properties of hubs
do not in general correlate with co-expression. Thus, we suggest that a
date/party dichotomy is not meaningful and it might be more useful to conceive
of roles for protein-protein interactions rather than individual proteins. We
find significant correlations between interaction centrality and the functional
similarity of the interacting proteins.Comment: 27 pages, 5 main figures, 4 supplementary figure
Graph Representation Learning in Biomedicine
Biomedical networks are universal descriptors of systems of interacting
elements, from protein interactions to disease networks, all the way to
healthcare systems and scientific knowledge. With the remarkable success of
representation learning in providing powerful predictions and insights, we have
witnessed a rapid expansion of representation learning techniques into
modeling, analyzing, and learning with such networks. In this review, we put
forward an observation that long-standing principles of networks in biology and
medicine -- while often unspoken in machine learning research -- can provide
the conceptual grounding for representation learning, explain its current
successes and limitations, and inform future advances. We synthesize a spectrum
of algorithmic approaches that, at their core, leverage graph topology to embed
networks into compact vector spaces, and capture the breadth of ways in which
representation learning is proving useful. Areas of profound impact include
identifying variants underlying complex traits, disentangling behaviors of
single cells and their effects on health, assisting in diagnosis and treatment
of patients, and developing safe and effective medicines
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