Publications by authors named "Nina Tubau Ribera"

3 Publications

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A single-cell RNA expression atlas of normal, preneoplastic and tumorigenic states in the human breast.

EMBO J 2021 Jun 5;40(11):e107333. Epub 2021 May 5.

ACRF Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Vic, Australia.

To examine global changes in breast heterogeneity across different states, we determined the single-cell transcriptomes of > 340,000 cells encompassing normal breast, preneoplastic BRCA1 tissue, the major breast cancer subtypes, and pairs of tumors and involved lymph nodes. Elucidation of the normal breast microenvironment revealed striking changes in the stroma of post-menopausal women. Single-cell profiling of 34 treatment-naive primary tumors, including estrogen receptor (ER) , HER2 , and triple-negative breast cancers, revealed comparable diversity among cancer cells and a discrete subset of cycling cells. The transcriptomes of preneoplastic BRCA1 tissue versus tumors highlighted global changes in the immune microenvironment. Within the tumor immune landscape, proliferative CD8 T cells characterized triple-negative and HER2 cancers but not ER tumors, while all subtypes comprised cycling tumor-associated macrophages, thus invoking potentially different immunotherapy targets. Copy number analysis of paired ER tumors and lymph nodes indicated seeding by genetically distinct clones or mass migration of primary tumor cells into axillary lymph nodes. This large-scale integration of patient samples provides a high-resolution map of cell diversity in normal and cancerous human breast.
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June 2021

Shape variation analyzer: a classifier for temporomandibular joint damaged by osteoarthritis.

Proc SPIE Int Soc Opt Eng 2019 Feb 13;10950. Epub 2019 Mar 13.

Dept. of Statistics and Operations Research, University of North Carolina at Chapel Hill, Chapel Hill, Hanes Hall, Campus Box 3260, NC, USA 27599.

We developed a deep learning neural network, the Shape Variation Analyzer (SVA), that allows disease staging of bony changes in temporomandibular joint (TMJ) osteoarthritis (OA). The sample was composed of 259 TMJ CBCT scans for the training set and 34 for the testing dataset. The 3D meshes had been previously classified in 6 groups by 2 expert clinicians. We improved the robustness of the training data using data augmentation, SMOTE, to alleviate over-fitting and to balance classes. We combined geometrical features and a shape descriptor, heat kernel signature, to describe every shape. The results were compared to nine different supervised machine learning algorithms. The deep learning neural network was the most accurate for classification of TMJ OA. In conclusion, SVA is a 3D Sheer extension that classifies pathology of the temporomandibular joint osteoarthritis cases based on 3D morphology.
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February 2019

A web-based system for neural network based classification in temporomandibular joint osteoarthritis.

Comput Med Imaging Graph 2018 07 1;67:45-54. Epub 2018 May 1.

Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.

Objective: The purpose of this study is to describe the methodological innovations of a web-based system for storage, integration and computation of biomedical data, using a training imaging dataset to remotely compute a deep neural network classifier of temporomandibular joint osteoarthritis (TMJOA).

Methods: This study imaging dataset consisted of three-dimensional (3D) surface meshes of mandibular condyles constructed from cone beam computed tomography (CBCT) scans. The training dataset consisted of 259 condyles, 105 from control subjects and 154 from patients with diagnosis of TMJ OA. For the image analysis classification, 34 right and left condyles from 17 patients (39.9 ± 11.7 years), who experienced signs and symptoms of the disease for less than 5 years, were included as the testing dataset. For the integrative statistical model of clinical, biological and imaging markers, the sample consisted of the same 17 test OA subjects and 17 age and sex matched control subjects (39.4 ± 15.4 years), who did not show any sign or symptom of OA. For these 34 subjects, a standardized clinical questionnaire, blood and saliva samples were also collected. The technological methodologies in this study include a deep neural network classifier of 3D condylar morphology (ShapeVariationAnalyzer, SVA), and a flexible web-based system for data storage, computation and integration (DSCI) of high dimensional imaging, clinical, and biological data.

Results: The DSCI system trained and tested the neural network, indicating 5 stages of structural degenerative changes in condylar morphology in the TMJ with 91% close agreement between the clinician consensus and the SVA classifier. The DSCI remotely ran with a novel application of a statistical analysis, the Multivariate Functional Shape Data Analysis, that computed high dimensional correlations between shape 3D coordinates, clinical pain levels and levels of biological markers, and then graphically displayed the computation results.

Conclusions: The findings of this study demonstrate a comprehensive phenotypic characterization of TMJ health and disease at clinical, imaging and biological levels, using novel flexible and versatile open-source tools for a web-based system that provides advanced shape statistical analysis and a neural network based classification of temporomandibular joint osteoarthritis.
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July 2018