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| Status |
Public on Sep 26, 2021 |
| Title |
FlowCT for the analysis of large immunophenotypic datasets and biomarker discovery in cancer immunology |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Large-scale immune monitoring is becoming routinely used in clinical trials to identify determinants of treatment responsiveness, particularly to immunotherapies. Flow cytometry remains one of the most versatile and high throughput approaches for single-cell analysis; however, manual interpretation of multidimensional data poses a challenge to capture full cellular diversity and provide reproducible results. We present FlowCT, a semi-automated workspace empowered to analyze large datasets that includes pre-processing, normalization, multiple dimensionality reduction techniques, automated clustering and predictive modeling tools. As a proof of concept, we used FlowCT to compare the T cell compartment in bone marrow (BM) vs peripheral blood (PB) of patients with smoldering multiple myeloma (MM); identify minimally-invasive immune biomarkers of progression from smoldering to active MM; define prognostic T cell subsets in the BM of patients with active MM after treatment intensification; and assess the longitudinal effect of maintenance therapy in BM T cells. A total of 354 samples were analyzed and immune signatures predictive of malignant transformation in 150 smoldering MM patients (hazard ratio [HR]: 1.7; P <.001), and of progression-free (HR: 4.09; P <.0001) and overall survival (HR: 3.12; P =.047) in 100 active MM patients, were identified. New data also emerged about stem cell memory T cells, the concordance between immune profiles in BM vs PB and the immunomodulatory effect of maintenance therapy. FlowCT is a new open-source computational approach that can be readily implemented by research laboratories to perform quality-control, analyze high-dimensional data, unveil cellular diversity and objectively identify biomarkers in large immune monitoring studies.
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| Overall design |
Ten T cell populations FACS sorted from 3 healthy donors
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| Contributor(s) |
Botta C, Maia C, Garcés J, Termini R, Pérez C, Manrique I, Burgos L, Zabaleta A, Alignani D, Sarvide S, Merino J, Puig N, Cedena M, Rossi M, Tassone P, Gentile M, Correale P, Borrello I, Terpos E, Jelinek T, Paiva A, Roccaro A, Goldschmidt H, Avet-Loiseau H, Rosiñol L, Mateos M, Martinez-Lopez J, Lahuerta J, Bladé J, San-Miguel JF, Paiva B |
| Citation(s) |
34587246 |
| Submission date |
Feb 12, 2021 |
| Last update date |
Dec 27, 2021 |
| Contact name |
Juan Jose Garces |
| E-mail(s) |
jgarces@unav.es
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| Organization name |
Clínica Universidad de Navarra - Centro de Investigación Médica Aplicada
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| Street address |
Av. Pío XII, 55
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| City |
Pamplona |
| State/province |
Navarra |
| ZIP/Postal code |
31008 |
| Country |
Spain |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (30)
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| GSM5079493 |
T cells CCR6 from healthy donor HD1 |
| GSM5079494 |
T cells central memory from healthy donor HD1 |
| GSM5079495 |
T cells CXCR3 CCR4 from healthy donor HD1 |
| GSM5079496 |
T cells naïve from healthy donor HD1 |
| GSM5079497 |
T cell helper 1 from healthy donor HD1 |
| GSM5079498 |
T cell helper 1_17 from healthy donor HD1 |
| GSM5079499 |
T cell helper 17 from healthy donor HD1 |
| GSM5079500 |
T cell helper 2 from healthy donor HD1 |
| GSM5079501 |
Transitional stem cell memory T cells CCR4 from healthy donor HD1 |
| GSM5079502 |
Transitional stem cell memory T cells CXCR3 from healthy donor HD1 |
| GSM5079503 |
T cells CCR6 from healthy donor HD2 |
| GSM5079504 |
T cells central memory from healthy donor HD2 |
| GSM5079505 |
T cells CXCR3 CCR4 from healthy donor HD2 |
| GSM5079506 |
T cells naïve from healthy donor HD2 |
| GSM5079507 |
T cell helper 1 from healthy donor HD2 |
| GSM5079508 |
T cell helper 1_17 from healthy donor HD2 |
| GSM5079509 |
T cell helper 17 from healthy donor HD2 |
| GSM5079510 |
T cell helper 2 from healthy donor HD2 |
| GSM5079511 |
Transitional stem cell memory T cells CCR4 from healthy donor HD2 |
| GSM5079512 |
Transitional stem cell memory T cells CXCR3 from healthy donor HD2 |
| GSM5079513 |
T cells CCR6 from healthy donor HD3 |
| GSM5079514 |
T cells central memory from healthy donor HD3 |
| GSM5079515 |
T cells CXCR3 CCR4 from healthy donor HD3 |
| GSM5079516 |
T cells naïve from healthy donor HD3 |
| GSM5079517 |
T cell helper 1 from healthy donor HD3 |
| GSM5079518 |
T cell helper 1_17 from healthy donor HD3 |
| GSM5079519 |
T cell helper 17 from healthy donor HD3 |
| GSM5079520 |
T cell helper 2 from healthy donor HD3 |
| GSM5079521 |
Transitional stem cell memory T cells CCR4 from healthy donor HD3 |
| GSM5079522 |
Transitional stem cell memory T cells CXCR3 from healthy donor HD3 |
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| Relations |
| BioProject |
PRJNA701666 |
| SRA |
SRP306235 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE166711_counts.cnt.txt.gz |
1.0 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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