4 research outputs found
Beyond Flatland : exploring graphs in many dimensions
Societies, technologies, economies, ecosystems, organisms, . . . Our world is composed of complex networksâsystems with many elements that interact in nontrivial ways. Graphs are natural models of these systems, and scientists have made tremendous progress in developing tools for their analysis. However, research has long focused on relatively simple graph representations and problem specifications, often discarding valuable real-world information in the process. In recent years, the limitations of this approach have become increasingly apparent, but we are just starting to comprehend how more intricate data representations and problem formulations might benefit our understanding of relational phenomena. Against this background, our thesis sets out to explore graphs in five dimensions: descriptivity, multiplicity, complexity, expressivity, and responsibility. Leveraging tools from graph theory, information theory, probability theory, geometry, and topology, we develop methods to (1) descriptively compare individual graphs, (2) characterize similarities and differences between groups of multiple graphs, (3) critically assess the complexity of relational data representations and their associated scientific culture, (4) extract expressive features from and for hypergraphs, and (5) responsibly mitigate the risks induced by graph-structured content recommendations. Thus, our thesis is naturally situated at the intersection of graph mining, graph learning, and network analysis.Gesellschaften, Technologien, Volkswirtschaften, Ăkosysteme, Organismen, . . . Unsere Welt besteht aus komplexen NetzwerkenâSystemen mit vielen Elementen, die auf nichttriviale Weise interagieren. Graphen sind natĂŒrliche Modelle dieser Systeme, und die Wissenschaft hat bei der Entwicklung von Methoden zu ihrer Analyse groĂe Fortschritte gemacht. Allerdings hat sich die Forschung lange auf relativ einfache GraphreprĂ€sentationen und Problemspezifikationen beschrĂ€nkt, oft unter VernachlĂ€ssigung wertvoller Informationen aus der realen Welt. In den vergangenen Jahren sind die Grenzen dieser Herangehensweise zunehmend deutlich geworden, aber wir beginnen gerade erst zu erfassen, wie unser VerstĂ€ndnis relationaler PhĂ€nomene von intrikateren DatenreprĂ€sentationen und Problemstellungen profitieren kann. Vor diesem Hintergrund erkundet unsere Dissertation Graphen in fĂŒnf Dimensionen: DeskriptivitĂ€t, MultiplizitĂ€t, KomplexitĂ€t, ExpressivitĂ€t, und Verantwortung. Mithilfe von Graphentheorie, Informationstheorie, Wahrscheinlichkeitstheorie, Geometrie und Topologie entwickeln wir Methoden, welche (1) einzelne Graphen deskriptiv vergleichen, (2) Gemeinsamkeiten und Unterschiede zwischen Gruppen multipler Graphen charakterisieren, (3) die KomplexitĂ€t relationaler DatenreprĂ€sentationen und der mit ihnen verbundenen Wissenschaftskultur kritisch beleuchten, (4) expressive Merkmale von und fĂŒr Hypergraphen extrahieren, und (5) verantwortungsvoll den Risiken begegnen, welche die Graphstruktur von Inhaltsempfehlungen mit sich bringt. Damit liegt unsere Dissertation naturgemÀà an der Schnittstelle zwischen Graph Mining, Graph Learning und Netzwerkanalyse
Computational approaches to discovering differentiation genes in the peripheral nervous system of drosophila melanogaster
In the common fruit fly, Drosophila melanogaster, neural cell fate specification is triggered by
a group of conserved transcriptional regulators known as proneural factors. Proneural factors
induce neural fate in uncommitted neuroectodermal progenitor cells, in a process that culminates
in sensory neuron differentiation. While the role of proneural factors in early fate specification
has been described, less is known about the transition between neural specification
and neural differentiation. The aim of this thesis is to use computational methods to improve
the understanding of terminal neural differentiation in the Peripheral Nervous System (PNS) of
Drosophila.
To provide an insight into how proneural factors coordinate the developmental programme
leading to neural differentiation, expression profiling covering the first 3 hours of PNS development
in Drosophila embryos had been previously carried out by Cachero et al. [2011]. The
study revealed a time-course of gene expression changes from specification to differentiation
and suggested a cascade model, whereby proneural factors regulate a group of intermediate
transcriptional regulators which are in turn responsible for the activation of specific differentiation
target genes.
In this thesis, I propose to select potentially important differentiation genes from the transcriptional
data in Cachero et al. [2011] using a novel approach centred on protein interaction
network-driven prioritisation. This is based on the insight that biological hypotheses supported
by diverse data sources can represent stronger candidates for follow-up studies. Specifically,
I propose the usage of protein interaction network data because of documented transcriptome-interactome
correlations, which suggest that differentially expressed genes encode products
that tend to belong to functionally related protein interaction clusters.
Experimental protein interaction data is, however, remarkably sparse. To increase the informative
power of protein-level analyses, I develop a novel approach to augment publicly
available protein interaction datasets using functional conservation between orthologous proteins
across different genomes, to predict interologs (interacting orthologs). I implement this
interolog retrieval methodology in a collection of open-source software modules called Bio::
Homology::InterologWalk, the first generalised framework using web-services for âon-the-
flyâ interolog projection. Bio::Homology::InterologWalk works with homology data
for any of the hundreds of genomes in Ensembl and Ensembgenomes Metazoa, and with experimental
protein interaction data curated by EBI Intact. It generates putative protein interactions
and optionally collates meta-data into a prioritisation index that can be used to help
select interologs with high experimental support. The methodology proposed represents a significant
advance over existing interolog data sources, which are restricted to specific biological
domains with fixed underlying data sources often only accessible through basic web-interfaces.
Using Bio::Homology::InterologWalk, I build interolog models in Drosophila sensory
neurons and, guided by the transcriptome data, find evidence implicating a small set of genes
in a conserved sensory neuronal specialisation dynamic, the assembly of the ciliary dendrite in
mechanosensory neurons. Using network community-finding algorithms I obtain functionally
enriched communities, which I analyse using an array of novel computational techniques. The
ensuing datasets lead to the elucidation of a cluster of interacting proteins encoded by the target
genes of one of the intermediate transcriptional regulators of neurogenesis and ciliogenesis,
fd3F. These targets are validated in vivo and result in improved knowledge of the important
target genes activated by the transcriptional cascade, suggesting a scenario for the mechanisms
orchestrating the ordered assembly of the cilium during differentiation
New Directions for Contact Integrators
Contact integrators are a family of geometric numerical schemes which
guarantee the conservation of the contact structure. In this work we review the
construction of both the variational and Hamiltonian versions of these methods.
We illustrate some of the advantages of geometric integration in the
dissipative setting by focusing on models inspired by recent studies in
celestial mechanics and cosmology.Comment: To appear as Chapter 24 in GSI 2021, Springer LNCS 1282