scholarly journals Topological data analysis identifies distinct biomarker phenotypes during the inflammatory phase of COVID-19

2021 ◽  
Author(s):  
Paul W Blair ◽  
Joost Brandsma ◽  
Josh G. Chenoweth ◽  
Stephanie A. Richard ◽  
Nusrat J. Epsi ◽  
...  
Keyword(s):  
Data Analysis ◽  
Dynamic Range ◽  
The United States ◽  
Topological Data Analysis ◽  
Severe Illness ◽  
Clustering Methods ◽  
Inflammatory Phase ◽  
Inflammatory Protein ◽  
Broad Dynamic Range ◽  
Topological Data

OBJECTIVES: The relationships between baseline clinical phenotypes and the cytokine milieu of the peak inflammatory phase of coronavirus 2019 (COVID-19) are not yet well understood. We used Topological Data Analysis (TDA), a dimensionality reduction technique to identify patterns of inflammation associated with COVID-19 severity and clinical characteristics. DESIGN: Exploratory analysis from a multi-center prospective cohort study. SETTING: Eight military hospitals across the United States between April 2020 and January 2021. PATIENTS: Adult (≥18 years of age) SARS-CoV-2 positive inpatient and outpatient participants were enrolled with plasma samples selected from the putative inflammatory phase of COVID-19, defined as 15-28 days post symptom onset. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Concentrations of 12 inflammatory protein biomarkers were measured using a broad dynamic range immunoassay. TDA identified 3 distinct inflammatory protein expression clusters. Peak severity (outpatient, hospitalized, ICU admission or death), Charlson Comorbidity Index (CCI), and body mass index (BMI) were evaluated with logistic regression for associations with each cluster. The study population (n=129, 33.3% female, median 41.3 years of age) included 77 outpatient, 31 inpatient, 16 ICU-level, and 5 fatal cases. Three distinct clusters were found that differed by peak disease severity (p <0.001), age (p <0.001), BMI (p<0.001), and CCI (p=0.001). CONCLUSIONS: Exploratory clustering methods can stratify heterogeneous patient populations and identify distinct inflammation patterns associated with comorbid disease, obesity, and severe illness due to COVID-19.

scholarly journals 438. Phenotypic Differences Between Distinct Immune Biomarker Clusters During the ‘Hyperinflammatory’ Middle-Phase of COVID-19

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S320-S321
Author(s):  
Paul W Blair ◽  
Joost Brandsma ◽  
Nusrat J Epsi ◽  
Stephanie A Richard ◽  
Deborah Striegel ◽  
...  
Keyword(s):  
Machine Learning ◽  
Data Analysis ◽  
Pulmonary Disease ◽  
The United States ◽  
Phase Iii ◽  
Severe Illness ◽  
Stepwise Logistic Regression ◽  
Chronic Pulmonary Disease ◽  
Middle Phase ◽  
Broad Dynamic Range

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections peak during an inflammatory ‘middle’ phase and lead to severe illness predominately among those with certain comorbid noncommunicable diseases (NCDs). We used network machine learning to identify inflammation biomarker patterns associated with COVID-19 among those with NCDs. Methods SARS-CoV-2 RT-PCR positive subjects who had specimens available within 15-28 days post-symptom onset were selected from the DoD/USU EPICC COVID-19 cohort study. Plasma levels of 15 inflammation protein biomarkers were measured using a broad dynamic range immunoassay on samples collected from individuals with COVID-19 at 8 military hospitals across the United States. A network machine learning algorithm, topological data analysis (TDA), was performed using results from the ‘hyperinflammatory’ middle phase. Backward selection stepwise logistic regression was used to identify analytes associated with each cluster. NCDs with a significant association (0.05 significance level) across clusters using Fisher’s exact test were further evaluated comparing the NCD frequency in each cluster against all other clusters using a Kruskal-Wallis test. A sensitivity analysis excluding mild disease was also performed. Results The analysis population (n=129, 33.3% female, median 41.3 years of age) included 77 ambulatory, 31 inpatient, 16 ICU-level, and 5 fatal cases. TDA identified 5 unique clusters (Figure 1). Stepwise regression with a Bonferroni-corrected cutoff adjusted for severity identified representative analytes for each cluster (Table 1). The frequency of diabetes (p=0.01), obesity (p&lt; 0.001), and chronic pulmonary disease (p&lt; 0.001) differed among clusters. When restricting to hospitalized patients, obesity (8 of 11), chronic pulmonary disease (6 of 11), and diabetes (6 of 11) were more prevalent in cluster C than all other clusters. Cluster differences in comorbid diseases and severity by cluster. 1A: bar plot of diabetes prevalence; 1B: bar plot of chronic lung disease ; 1C: bar plot of obesity prevalence; 1D: prevalence of steroid treatment ; 1E: Topologic data analysis network with clusters labeled; 1F: Bar plot of ordinal levels of severity. Conclusion Machine learning clustering methods are promising analytical tools for identifying inflammation marker patterns associated with baseline risk factors and severe illness due to COVID-19. These approaches may offer new insights for COVID19 prognosis, therapy, and prevention. Disclosures Simon Pollett, MBBS, Astra Zeneca (Other Financial or Material Support, HJF, in support of USU IDCRP, funded under a CRADA to augment the conduct of an unrelated Phase III COVID-19 vaccine trial sponsored by AstraZeneca as part of USG response (unrelated work))

scholarly journals Topological Data Analysis Approaches to Uncovering the Timing of Ring Structure Onset in Filamentous Networks

2021 ◽  
Vol 83 (3) ◽  
Author(s):  
Maria-Veronica Ciocanel ◽  
Riley Juenemann ◽  
Adriana T. Dawes ◽  
Scott A. McKinley
Keyword(s):  
Time Series ◽  
Data Analysis ◽  
Actin Filaments ◽  
Time Series Data ◽  
Polymer Networks ◽  
Topological Data Analysis ◽  
Series Data ◽  
Topological Features ◽  
Topological Data

AbstractIn developmental biology as well as in other biological systems, emerging structure and organization can be captured using time-series data of protein locations. In analyzing this time-dependent data, it is a common challenge not only to determine whether topological features emerge, but also to identify the timing of their formation. For instance, in most cells, actin filaments interact with myosin motor proteins and organize into polymer networks and higher-order structures. Ring channels are examples of such structures that maintain constant diameters over time and play key roles in processes such as cell division, development, and wound healing. Given the limitations in studying interactions of actin with myosin in vivo, we generate time-series data of protein polymer interactions in cells using complex agent-based models. Since the data has a filamentous structure, we propose sampling along the actin filaments and analyzing the topological structure of the resulting point cloud at each time. Building on existing tools from persistent homology, we develop a topological data analysis (TDA) method that assesses effective ring generation in this dynamic data. This method connects topological features through time in a path that corresponds to emergence of organization in the data. In this work, we also propose methods for assessing whether the topological features of interest are significant and thus whether they contribute to the formation of an emerging hole (ring channel) in the simulated protein interactions. In particular, we use the MEDYAN simulation platform to show that this technique can distinguish between the actin cytoskeleton organization resulting from distinct motor protein binding parameters.

scholarly journals Classification of apatite structures via topological data analysis: a framework for a ‘Materials Barcode’ representation of structure maps

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Scott Broderick ◽  
Ruhil Dongol ◽  
Tianmu Zhang ◽  
Krishna Rajan
Keyword(s):  
Machine Learning ◽  
Data Analysis ◽  
Crystal Chemistry ◽  
Persistent Homology ◽  
Hierarchical Classification ◽  
Topological Data Analysis ◽  
Learning Tool ◽  
Coordination Polyhedra ◽  
Machine Learning Tool ◽  
Topological Data

AbstractThis paper introduces the use of topological data analysis (TDA) as an unsupervised machine learning tool to uncover classification criteria in complex inorganic crystal chemistries. Using the apatite chemistry as a template, we track through the use of persistent homology the topological connectivity of input crystal chemistry descriptors on defining similarity between different stoichiometries of apatites. It is shown that TDA automatically identifies a hierarchical classification scheme within apatites based on the commonality of the number of discrete coordination polyhedra that constitute the structural building units common among the compounds. This information is presented in the form of a visualization scheme of a barcode of homology classifications, where the persistence of similarity between compounds is tracked. Unlike traditional perspectives of structure maps, this new “Materials Barcode” schema serves as an automated exploratory machine learning tool that can uncover structural associations from crystal chemistry databases, as well as to achieve a more nuanced insight into what defines similarity among homologous compounds.

The Shape of Things: Topological Data Analysis

CHANCE ◽  
2021 ◽  
Vol 34 (2) ◽  
pp. 59-64
Author(s):  
Nicole Lazar ◽  
Hyunnam Ryu
Keyword(s):  
Data Analysis ◽  
Topological Data Analysis ◽  
Topological Data

scholarly journals Empowering Advanced Driver-Assistance Systems from Topological Data Analysis

Mathematics ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 634
Author(s):  
Tarek Frahi ◽  
Francisco Chinesta ◽  
Antonio Falcó ◽  
Alberto Badias ◽  
Elias Cueto ◽  
...  
Keyword(s):  
Data Analysis ◽  
The State ◽  
Sensor Data ◽  
Topological Data Analysis ◽  
Motion Sensors ◽  
Driver Assistance Systems ◽  
The Road ◽  
Topological Features ◽  
Recent Developments ◽  
Topological Data

We are interested in evaluating the state of drivers to determine whether they are attentive to the road or not by using motion sensor data collected from car driving experiments. That is, our goal is to design a predictive model that can estimate the state of drivers given the data collected from motion sensors. For that purpose, we leverage recent developments in topological data analysis (TDA) to analyze and transform the data coming from sensor time series and build a machine learning model based on the topological features extracted with the TDA. We provide some experiments showing that our model proves to be accurate in the identification of the state of the user, predicting whether they are relaxed or tense.

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