1,963 research outputs found
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
Exploiting single-cell expression to characterize co-expression replicability
BACKGROUND: Co-expression networks have been a useful tool for functional genomics, providing important clues about the cellular and biochemical mechanisms that are active in normal and disease processes. However, co-expression analysis is often treated as a black box with results being hard to trace to their basis in the data. Here, we use both published and novel single-cell RNA sequencing (RNA-seq) data to understand fundamental drivers of gene-gene connectivity and replicability in co-expression networks. RESULTS: We perform the first major analysis of single-cell co-expression, sampling from 31 individual studies. Using neighbor voting in cross-validation, we find that single-cell network connectivity is less likely to overlap with known functions than co-expression derived from bulk data, with functional variation within cell types strongly resembling that also occurring across cell types. To identify features and analysis practices that contribute to this connectivity, we perform our own single-cell RNA-seq experiment of 126 cortical interneurons in an experimental design targeted to co-expression. By assessing network replicability, semantic similarity and overall functional connectivity, we identify technical factors influencing co-expression and suggest how they can be controlled for. Many of the technical effects we identify are expression-level dependent, making expression level itself highly predictive of network topology. We show this occurs generally through re-analysis of the BrainSpan RNA-seq data. CONCLUSIONS: Technical properties of single-cell RNA-seq data create confounds in co-expression networks which can be identified and explicitly controlled for in any supervised analysis. This is useful both in improving co-expression performance and in characterizing single-cell data in generally applicable terms, permitting cross-laboratory comparison within a common framework
Resolving Structure in Human Brain Organization: Identifying Mesoscale Organization in Weighted Network Representations
Human brain anatomy and function display a combination of modular and
hierarchical organization, suggesting the importance of both cohesive
structures and variable resolutions in the facilitation of healthy cognitive
processes. However, tools to simultaneously probe these features of brain
architecture require further development. We propose and apply a set of methods
to extract cohesive structures in network representations of brain connectivity
using multi-resolution techniques. We employ a combination of soft
thresholding, windowed thresholding, and resolution in community detection,
that enable us to identify and isolate structures associated with different
weights. One such mesoscale structure is bipartivity, which quantifies the
extent to which the brain is divided into two partitions with high connectivity
between partitions and low connectivity within partitions. A second,
complementary mesoscale structure is modularity, which quantifies the extent to
which the brain is divided into multiple communities with strong connectivity
within each community and weak connectivity between communities. Our methods
lead to multi-resolution curves of these network diagnostics over a range of
spatial, geometric, and structural scales. For statistical comparison, we
contrast our results with those obtained for several benchmark null models. Our
work demonstrates that multi-resolution diagnostic curves capture complex
organizational profiles in weighted graphs. We apply these methods to the
identification of resolution-specific characteristics of healthy weighted graph
architecture and altered connectivity profiles in psychiatric disease.Comment: Comments welcom
Learning and comparing functional connectomes across subjects
Functional connectomes capture brain interactions via synchronized
fluctuations in the functional magnetic resonance imaging signal. If measured
during rest, they map the intrinsic functional architecture of the brain. With
task-driven experiments they represent integration mechanisms between
specialized brain areas. Analyzing their variability across subjects and
conditions can reveal markers of brain pathologies and mechanisms underlying
cognition. Methods of estimating functional connectomes from the imaging signal
have undergone rapid developments and the literature is full of diverse
strategies for comparing them. This review aims to clarify links across
functional-connectivity methods as well as to expose different steps to perform
a group study of functional connectomes
Interpretable statistics for complex modelling: quantile and topological learning
As the complexity of our data increased exponentially in the last decades, so has our
need for interpretable features. This thesis revolves around two paradigms to approach
this quest for insights.
In the first part we focus on parametric models, where the problem of interpretability
can be seen as a “parametrization selection”. We introduce a quantile-centric
parametrization and we show the advantages of our proposal in the context of regression,
where it allows to bridge the gap between classical generalized linear (mixed)
models and increasingly popular quantile methods.
The second part of the thesis, concerned with topological learning, tackles the
problem from a non-parametric perspective. As topology can be thought of as a way
of characterizing data in terms of their connectivity structure, it allows to represent
complex and possibly high dimensional through few features, such as the number of
connected components, loops and voids. We illustrate how the emerging branch of
statistics devoted to recovering topological structures in the data, Topological Data
Analysis, can be exploited both for exploratory and inferential purposes with a special
emphasis on kernels that preserve the topological information in the data.
Finally, we show with an application how these two approaches can borrow strength
from one another in the identification and description of brain activity through fMRI
data from the ABIDE project
Brain connectomics' modification to clarify motor and nonmotor features of myotonic dystrophy type 1
The adult form of myotonic dystrophy type 1 (DM1) presents with paradoxical inconsistencies between severity of brain damage, relative preservation of cognition, and failure in everyday life. This study, based on the assessment of brain connectivity and mechanisms of plasticity, aimed at reconciling these conflicting issues. Resting-state functional MRI and graph theoretical methods of analysis were used to assess brain topological features in a large cohort of patients with DM1. Patients, compared to controls, revealed reduced connectivity in a large frontoparietal network that correlated with their isolated impairment in visuospatial reasoning. Despite a global preservation of the topological properties, peculiar patterns of frontal disconnection and increased parietal-cerebellar connectivity were also identified in patients' brains. The balance between loss of connectivity and compensatory mechanisms in different brain networks might explain the paradoxical mismatch between structural brain damage and minimal cognitive deficits observed in these patients. This study provides a comprehensive assessment of brain abnormalities that fit well with both motor and nonmotor clinical features experienced by patients in their everyday life. The current findings suggest that measures of functional connectivity may offer the possibility of characterizing individual patients with the potential to become a clinical tool
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