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  1. Book ; Online: Observability of Hypergraphs

    Pickard, Joshua / Surana, Amit / Bloch, Anthony / Rajapakse, Indika

    2023  

    Abstract: In this paper we develop a framework to study observability for uniform hypergraphs. Hypergraphs are generalizations of graphs in which edges may connect any number of nodes, thereby representing multi-way relationships which are ubiquitous in many real- ... ...

    Abstract In this paper we develop a framework to study observability for uniform hypergraphs. Hypergraphs are generalizations of graphs in which edges may connect any number of nodes, thereby representing multi-way relationships which are ubiquitous in many real-world networks including neuroscience, social networks, and bioinformatics. We define a canonical multilinear dynamical system with linear outputs on uniform hypergraphs which captures such multi-way interactions and results in a homogeneous polynomial system. We derive a Kalman-rank-like condition for assessing the local weak observability of this resulting system and propose techniques for its efficient computation. We also propose a greedy heuristic to determine the minimum set of observable nodes, and demonstrate our approach numerically on different hypergraph topologies, and hypergraphs derived from an experimental biological dataset.

    Comment: 7 pages, 3 figures, 2 algorithms, lots of math!
    Keywords Mathematics - Dynamical Systems ; Electrical Engineering and Systems Science - Systems and Control
    Subject code 006
    Publishing date 2023-04-10
    Publishing country us
    Document type Book ; Online
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  2. Article ; Online: A lipid-associated macrophage lineage rewires the spatial landscape of adipose tissue in early obesity.

    Stansbury, Cooper M / Dotson, Gabrielle A / Pugh, Harrison / Rehemtulla, Alnawaz / Rajapakse, Indika / Muir, Lindsey A

    JCI insight

    2023  Volume 8, Issue 19

    Abstract: Adipose tissue macrophage (ATM) infiltration is associated with adipose tissue dysfunction and insulin resistance in mice and humans. Recent single-cell data highlight increased ATM heterogeneity in obesity but do not provide a spatial context for ATM ... ...

    Abstract Adipose tissue macrophage (ATM) infiltration is associated with adipose tissue dysfunction and insulin resistance in mice and humans. Recent single-cell data highlight increased ATM heterogeneity in obesity but do not provide a spatial context for ATM phenotype dynamics. We integrated single-cell RNA-Seq, spatial transcriptomics, and imaging of murine adipose tissue in a time course study of diet-induced obesity. Overall, proinflammatory immune cells were predominant in early obesity, whereas nonresident antiinflammatory ATMs predominated in chronic obesity. A subset of these antiinflammatory ATMs were transcriptomically intermediate between monocytes and mature lipid-associated macrophages (LAMs) and were consistent with a LAM precursor (pre-LAM). Pre-LAMs were spatially associated with early obesity crown-like structures (CLSs), which indicate adipose tissue dysfunction. Spatial data showed colocalization of ligand-receptor transcripts related to lipid signaling among monocytes, pre-LAMs, and LAMs, including Apoe, Lrp1, Lpl, and App. Pre-LAM expression of these ligands in early obesity suggested signaling to LAMs in the CLS microenvironment. Our results refine understanding of ATM diversity and provide insight into the dynamics of the LAM lineage during development of metabolic disease.
    MeSH term(s) Humans ; Mice ; Animals ; Adipose Tissue/metabolism ; Obesity/metabolism ; Macrophages/metabolism ; Diet ; Lipids
    Chemical Substances Lipids
    Language English
    Publishing date 2023-10-09
    Publishing country United States
    Document type Journal Article
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.171701
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  3. Article ; Online: A unified approach of detecting phase transition in time-varying complex networks.

    Znaidi, Mohamed Ridha / Sia, Jayson / Ronquist, Scott / Rajapakse, Indika / Jonckheere, Edmond / Bogdan, Paul

    Scientific reports

    2023  Volume 13, Issue 1, Page(s) 17948

    Abstract: Deciphering the non-trivial interactions and mechanisms driving the evolution of time-varying complex networks (TVCNs) plays a crucial role in designing optimal control strategies for such networks or enhancing their causal predictive capabilities. In ... ...

    Abstract Deciphering the non-trivial interactions and mechanisms driving the evolution of time-varying complex networks (TVCNs) plays a crucial role in designing optimal control strategies for such networks or enhancing their causal predictive capabilities. In this paper, we advance the science of TVCNs by providing a mathematical framework through which we can gauge how local changes within a complex weighted network affect its global properties. More precisely, we focus on unraveling unknown geometric properties of a network and determine its implications on detecting phase transitions within the dynamics of a TVCN. In this vein, we aim at elaborating a novel and unified approach that can be used to depict the relationship between local interactions in a complex network and its global kinetics. We propose a geometric-inspired framework to characterize the network's state and detect a phase transition between different states, to infer the TVCN's dynamics. A phase of a TVCN is determined by its Forman-Ricci curvature property. Numerical experiments show the usefulness of the proposed curvature formalism to detect the transition between phases within artificially generated networks. Furthermore, we demonstrate the effectiveness of the proposed framework in identifying the phase transition phenomena governing the training and learning processes of artificial neural networks. Moreover, we exploit this approach to investigate the phase transition phenomena in cellular re-programming by interpreting the dynamics of Hi-C matrices as TVCNs and observing singularity trends in the curvature network entropy. Finally, we demonstrate that this curvature formalism can detect a political change. Specifically, our framework can be applied to the US Senate data to detect a political change in the United States of America after the 1994 election, as discussed by political scientists.
    Language English
    Publishing date 2023-10-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-023-44791-3
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  4. Article ; Online: HAT: Hypergraph analysis toolbox.

    Pickard, Joshua / Chen, Can / Salman, Rahmy / Stansbury, Cooper / Kim, Sion / Surana, Amit / Bloch, Anthony / Rajapakse, Indika

    PLoS computational biology

    2023  Volume 19, Issue 6, Page(s) e1011190

    Abstract: Recent advances in biological technologies, such as multi-way chromosome conformation capture (3C), require development of methods for analysis of multi-way interactions. Hypergraphs are mathematically tractable objects that can be utilized to precisely ... ...

    Abstract Recent advances in biological technologies, such as multi-way chromosome conformation capture (3C), require development of methods for analysis of multi-way interactions. Hypergraphs are mathematically tractable objects that can be utilized to precisely represent and analyze multi-way interactions. Here we present the Hypergraph Analysis Toolbox (HAT), a software package for visualization and analysis of multi-way interactions in complex systems.
    MeSH term(s) Chromosomes ; Software
    Language English
    Publishing date 2023-06-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1011190
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  5. Article ; Online: Understanding memory B cell selection.

    Lindsly, Stephen / Gupta, Maya / Stansbury, Cooper / Rajapakse, Indika

    Journal of theoretical biology

    2021  Volume 531, Page(s) 110905

    Abstract: The mammalian adaptive immune system has evolved over millions of years to become an incredibly effective defense against foreign antigens. The adaptive immune system's humoral response creates plasma B cells and memory B cells, each with their own ... ...

    Abstract The mammalian adaptive immune system has evolved over millions of years to become an incredibly effective defense against foreign antigens. The adaptive immune system's humoral response creates plasma B cells and memory B cells, each with their own immunological objectives. The affinity maturation process is widely viewed as a heuristic to solve the global optimization problem of finding B cells with high affinity to the antigen. However, memory B cells appear to be purposely selected earlier in the affinity maturation process and have lower affinity. We propose that this memory B cell selection process may be an approximate solution to two optimization problems: optimizing for affinity to similar antigens in the future despite mutations or other minor differences, and optimizing to warm start the generation of plasma B cells in the future. We use simulations to provide evidence for our hypotheses, taking into account data showing that certain B cell mutations are more likely than others. Our findings are consistent with memory B cells having high-affinity to mutated antigens, but do not provide strong evidence that memory B cells will be more useful than selected naive B cells for seeding the secondary germinal centers.
    MeSH term(s) Adaptive Immunity ; Animals ; Antigens ; B-Lymphocytes ; Germinal Center ; Immunologic Memory
    Chemical Substances Antigens
    Language English
    Publishing date 2021-09-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2972-5
    ISSN 1095-8541 ; 0022-5193
    ISSN (online) 1095-8541
    ISSN 0022-5193
    DOI 10.1016/j.jtbi.2021.110905
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    Zs.A 923: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: The 4D Nucleome.

    Ried, Thomas / Rajapakse, Indika

    Methods (San Diego, Calif.)

    2017  Volume 123, Page(s) 1–2

    MeSH term(s) Animals ; Cell Nucleus/chemistry ; Cell Nucleus/physiology ; Genome, Human/physiology ; Humans ; Molecular Imaging/methods ; Molecular Imaging/trends
    Language English
    Publishing date 2017-07-19
    Publishing country United States
    Document type Editorial ; Introductory Journal Article
    ZDB-ID 1066584-5
    ISSN 1095-9130 ; 1046-2023
    ISSN (online) 1095-9130
    ISSN 1046-2023
    DOI 10.1016/j.ymeth.2017.06.031
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    Zs.A 3239: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
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  7. Article ; Online: Network dynamics of hypothalamic feeding neurons.

    Sweeney, Patrick / Chen, Can / Rajapakse, Indika / Cone, Roger D

    Proceedings of the National Academy of Sciences of the United States of America

    2021  Volume 118, Issue 14

    Abstract: Mutations in the melanocortin 4 receptor (MC4R) result in hyperphagia and obesity and are the most common cause of monogenic obesity in humans. Preclinical rodent studies have determined that the critical role of the MC4R in controlling feeding can be ... ...

    Abstract Mutations in the melanocortin 4 receptor (MC4R) result in hyperphagia and obesity and are the most common cause of monogenic obesity in humans. Preclinical rodent studies have determined that the critical role of the MC4R in controlling feeding can be mapped in part to its expression in the paraventricular nucleus of the hypothalamus (paraventricular nucleus [PVN]), where it regulates the activity of anorexic neural circuits. Despite the critical role of PVN MC4R neurons in regulating feeding, the in vivo neuronal activity of these cells remains largely unstudied, and the network activity of PVN MC4R neurons has not been determined. Here, we utilize in vivo single-cell endomicroscopic and mathematical approaches to determine the activity and network dynamics of PVN MC4R neurons in response to changes in energy state and pharmacological manipulation of central melanocortin receptors. We determine that PVN MC4R neurons exhibit both quantitative and qualitative changes in response to fasting and refeeding. Pharmacological stimulation of MC4R with the therapeutic MC4R agonist setmelanotide rapidly increases basal PVN MC4R activity, while stimulation of melanocortin 3 receptor (MC3R) inhibits PVN MC4R activity. Finally, we find that distinct PVN MC4R neuronal ensembles encode energy deficit and energy surfeit and that energy surfeit is associated with enhanced network connections within PVN MC4R neurons. These findings provide valuable insight into the neural dynamics underlying hunger and energy surfeit.
    MeSH term(s) Animals ; Feeding Behavior/physiology ; Male ; Mice ; Microscopy, Fluorescence ; Nerve Net ; Optical Imaging ; Paraventricular Hypothalamic Nucleus/cytology ; Paraventricular Hypothalamic Nucleus/physiology ; Receptor, Melanocortin, Type 3/agonists ; Receptor, Melanocortin, Type 4/metabolism ; Single-Cell Analysis
    Chemical Substances MC4R protein, mouse ; Mc3r protein, mouse ; Receptor, Melanocortin, Type 3 ; Receptor, Melanocortin, Type 4
    Language English
    Publishing date 2021-08-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2011140118
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    Zs.A 1148: Show issues Location:
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  8. Article ; Online: Emergence of function from coordinated cells in a tissue.

    Rajapakse, Indika / Smale, Stephen

    Proceedings of the National Academy of Sciences of the United States of America

    2017  Volume 114, Issue 7, Page(s) 1462–1467

    Abstract: This work presents a mathematical study of tissue dynamics. We combine within-cell genome dynamics and diffusion between cells, so that the synthesis of the two gives rise to the emergence of function, akin to establishing "tissue homeostasis." We ... ...

    Abstract This work presents a mathematical study of tissue dynamics. We combine within-cell genome dynamics and diffusion between cells, so that the synthesis of the two gives rise to the emergence of function, akin to establishing "tissue homeostasis." We introduce two concepts, monotonicity and a weak version of hardwiring. These together are sufficient for global convergence of the tissue dynamics.
    MeSH term(s) Algorithms ; Cell Communication ; Cell Physiological Phenomena ; Cells/metabolism ; Diffusion ; Genome ; Homeostasis ; Models, Biological ; Morphogenesis
    Language English
    Publishing date 2017-01-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1621145114
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    Zs.A 1148: Show issues Location:
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  9. Book ; Online: Hypergraph Dissimilarity Measures

    Surana, Amit / Chen, Can / Rajapakse, Indika

    2021  

    Abstract: In this paper, we propose two novel approaches for hypergraph comparison. The first approach transforms the hypergraph into a graph representation for use of standard graph dissimilarity measures. The second approach exploits the mathematics of tensors ... ...

    Abstract In this paper, we propose two novel approaches for hypergraph comparison. The first approach transforms the hypergraph into a graph representation for use of standard graph dissimilarity measures. The second approach exploits the mathematics of tensors to intrinsically capture multi-way relations. For each approach, we present measures that assess hypergraph dissimilarity at a specific scale or provide a more holistic multi-scale comparison. We test these measures on synthetic hypergraphs and apply them to biological datasets.
    Keywords Computer Science - Machine Learning
    Publishing date 2021-06-15
    Publishing country us
    Document type Book ; Online
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  10. Article ; Online: A lipid-associated macrophage lineage rewires the spatial landscape of adipose tissue in early obesity

    Cooper M. Stansbury / Gabrielle A. Dotson / Harrison Pugh / Alnawaz Rehemtulla / Indika Rajapakse / Lindsey A. Muir

    JCI Insight, Vol 8, Iss

    2023  Volume 19

    Abstract: Adipose tissue macrophage (ATM) infiltration is associated with adipose tissue dysfunction and insulin resistance in mice and humans. Recent single-cell data highlight increased ATM heterogeneity in obesity but do not provide a spatial context for ATM ... ...

    Abstract Adipose tissue macrophage (ATM) infiltration is associated with adipose tissue dysfunction and insulin resistance in mice and humans. Recent single-cell data highlight increased ATM heterogeneity in obesity but do not provide a spatial context for ATM phenotype dynamics. We integrated single-cell RNA-Seq, spatial transcriptomics, and imaging of murine adipose tissue in a time course study of diet-induced obesity. Overall, proinflammatory immune cells were predominant in early obesity, whereas nonresident antiinflammatory ATMs predominated in chronic obesity. A subset of these antiinflammatory ATMs were transcriptomically intermediate between monocytes and mature lipid-associated macrophages (LAMs) and were consistent with a LAM precursor (pre-LAM). Pre-LAMs were spatially associated with early obesity crown-like structures (CLSs), which indicate adipose tissue dysfunction. Spatial data showed colocalization of ligand-receptor transcripts related to lipid signaling among monocytes, pre-LAMs, and LAMs, including Apoe, Lrp1, Lpl, and App. Pre-LAM expression of these ligands in early obesity suggested signaling to LAMs in the CLS microenvironment. Our results refine understanding of ATM diversity and provide insight into the dynamics of the LAM lineage during development of metabolic disease.
    Keywords Metabolism ; Medicine ; R
    Language English
    Publishing date 2023-10-01T00:00:00Z
    Publisher American Society for Clinical investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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