{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:22:20Z","timestamp":1772252540979,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Georgia Cancer Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Patients are complex and heterogeneous; clinical data sets are complicated by noise, missing data, and the presence of mixed-type data. Using such data sets requires understanding the high-dimensional \u201cspace of patients\u201d, composed of all measurements that define all relevant phenotypes. The current state-of-the-art merely defines spatial groupings of patients using cluster analyses. Our goal is to apply topological data analysis (TDA), a new unsupervised technique, to obtain a more complete understanding of patient space. We applied TDA to a space of 266 previously untreated patients with Chronic Lymphocytic Leukemia (CLL), using the \u201cdaisy\u201d metric to compute distances between clinical records. We found clear evidence for both loops and voids in the CLL data. To interpret these structures, we developed novel computational and graphical methods. The most persistent loop and the most persistent void can be explained using three dichotomized, prognostically important factors in CLL: IGHV somatic mutation status, beta-2 microglobulin, and Rai stage. In conclusion, patient space turns out to be richer and more complex than current models suggest. TDA could become a powerful tool in a researcher\u2019s arsenal for interpreting high-dimensional data by providing novel insights into biological processes and improving our understanding of clinical and biological data sets.<\/jats:p>","DOI":"10.3390\/cancers16152662","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T09:22:42Z","timestamp":1721985762000},"page":"2662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Topological Structures in the Space of Treatment-Na\u00efve Patients with Chronic Lymphocytic Leukemia"],"prefix":"10.3390","volume":"16","author":[{"suffix":"II","given":"Reginald L.","family":"McGee","sequence":"first","affiliation":[{"name":"Department of Mathematics and Statistics, Haverford College, Haverford, PA 19041, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jake","family":"Reed","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Data Science, and Epidemiology, Georgia Cancer Center at Augusta University, Augusta, GA 30912, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caitlin E.","family":"Coombes","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Stanford University, Palo Alto, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4223-5316","authenticated-orcid":false,"given":"Carmen D.","family":"Herling","sequence":"additional","affiliation":[{"name":"Clinic of Hematology, Cellular Therapy, Hemostaseology, and Infectious Diseases, University of Leipzig, 04103 Leipzig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Keating","sequence":"additional","affiliation":[{"name":"Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynne V.","family":"Abruzzo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7630-2123","authenticated-orcid":false,"given":"Kevin R.","family":"Coombes","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Data Science, and Epidemiology, Georgia Cancer Center at Augusta University, Augusta, GA 30912, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,26]]},"reference":[{"key":"ref_1","first-page":"425","article-title":"On distance computation in space of mixed-type variables in medical data mining","volume":"90","author":"Juhola","year":"2002","journal-title":"Stud. 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