Mesenchymal-like immune-altered is the fourth robust triple-negative breast cancer molecular subtype.

BACKGROUND: Robust molecular subtyping of triple-negative breast cancer (TNBC) is a prerequisite for the success of precision medicine. Today, there is a clear consensus on three TNBC molecular subtypes: luminal androgen receptor (LAR), basal-like immune-activated (BLIA), and basal-like immune-suppressed (BLIS). However, the debate about the robustness of other subtypes is still open. METHODS: An unprecedented number (n = 1942) of TNBC patient data was collected. Microarray- and RNAseq-based cohorts were independently investigated. Unsupervised analyses were conducted using k-means consensus clustering. Clusters of patients were then functionally annotated using different approaches. Prediction of response to chemotherapy and targeted therapies, immune checkpoint blockade, and radiotherapy were also screened for each TNBC subtype. RESULTS: Four TNBC subtypes were identified in the cohort: LAR (19.36%); mesenchymal stem-like (MSL/MES) (17.35%); BLIA (31.06%); and BLIS (32.23%). Regarding the MSL/MES subtype, we suggest renaming it to mesenchymal-like immune-altered (MLIA) to emphasize its specific histological background and nature of immune response. Treatment response prediction results show, among other things, that despite immune activation, immune checkpoint blockade is probably less or completely ineffective in MLIA, possibly caused by mesenchymal background and/or an enrichment in dysfunctional cytotoxic T lymphocytes. TNBC subtyping results were included in the bc-GenExMiner v5.0 webtool ( http://bcgenex.ico.unicancer.fr ). CONCLUSION: The mesenchymal TNBC subtype is characterized by an exhausted and altered immune response, and resistance to immune checkpoint inhibitors. Consensus for molecular classification of TNBC subtyping and prediction of cancer treatment responses helps usher in the era of precision medicine for TNBC patients.

Bayesian hierarchical models for the prediction of the driver flow and passenger waiting times in a stochastic carpooling service.

Carpooling is an integral component in smart carbon-neutral cities, in particular to facilitate home-work commuting. We study an innovative carpooling service which offers stochastic passenger-driver matching. Stochastic matching is when a passenger makes a carpooling request, and then waits for the first driver from a population of drivers who are already en route. Crucially a designated driver is not assigned as in a traditional carpooling service. For this new form of stochastic carpooling, we propose a two-stage Bayesian hierarchical model to predict the driver flow and the passenger waiting times. The first stage focuses on prediction of the aggregated daily driver flows, and the second stage processes these daily driver flow into hourly predictions of the passenger waiting times. We demonstrate, for an operational carpooling service, that the predictions from our Bayesian hierarchical model outperform the predictions from a frequentist model and a Bayesian non-hierarchical model. The inferences from our proposed model provide insights for the service operator in their evidence-based decision making.

An Introduction to Topological Data Analysis: Fundamental and Practical Aspects for Data Scientists.

With the recent explosion in the amount, the variety, and the dimensionality of available data, identifying, extracting, and exploiting their underlying structure has become a problem of fundamental importance for data analysis and statistical learning. Topological data analysis (tda) is a recent and fast-growing field providing a set of new topological and geometric tools to infer relevant features for possibly complex data. It proposes new well-founded mathematical theories and computational tools that can be used independently or in combination with other data analysis and statistical learning techniques. This article is a brief introduction, through a few selected topics, to basic fundamental and practical aspects of tda for nonexperts.

Identifying homogeneous subgroups of patients and important features: a topological machine learning approach.

BACKGROUND: This paper exploits recent developments in topological data analysis to present a pipeline for clustering based on Mapper, an algorithm that reduces complex data into a one-dimensional graph. RESULTS: We present a pipeline to identify and summarise clusters based on statistically significant topological features from a point cloud using Mapper. CONCLUSIONS: Key strengths of this pipeline include the integration of prior knowledge to inform the clustering process and the selection of optimal clusters; the use of the bootstrap to restrict the search to robust topological features; the use of machine learning to inspect clusters; and the ability to incorporate mixed data types. Our pipeline can be downloaded under the GNU GPLv3 license at https://github.com/kcl-bhi/mapper-pipeline .

Development of an absolute assignment predictor for triple-negative breast cancer subtyping using machine learning approaches.

Triple-negative breast cancer (TNBC) heterogeneity represents one of the main obstacles to precision medicine for this disease. Recent concordant transcriptomics studies have shown that TNBC could be divided into at least three subtypes with potential therapeutic implications. Although a few studies have been conducted to predict TNBC subtype using transcriptomics data, the subtyping was partially sensitive and limited by batch effect and dependence on a given dataset, which may penalize the switch to routine diagnostic testing. Therefore, we sought to build an absolute predictor (i.e., intra-patient diagnosis) based on machine learning algorithms with a limited number of probes. To that end, we started by introducing probe binary comparison for each patient (indicators). We based the predictive analysis on this transformed data. Probe selection was first involved combining both filter and wrapper methods for variable selection using cross-validation. We tested three prediction models (random forest, gradient boosting [GB], and extreme gradient boosting) using this optimal subset of indicators as inputs. Nested cross-validation consistently allowed us to choose the best model. The results showed that the fifty selected indicators highlighted the biological characteristics associated with each TNBC subtype. The GB based on this subset of indicators performs better than other models.

Robust Stride Detector from Ankle-Mounted Inertial Sensors for Pedestrian Navigation and Activity Recognition with Machine Learning Approaches.

In this paper, a stride detector algorithm combined with a technique inspired by zero velocity update (ZUPT) is proposed to reconstruct the trajectory of a pedestrian from an ankle-mounted inertial device. This innovative approach is based on sensor alignment and machine learning. It is able to detect 100% of both normal walking strides and more than 97% of atypical strides such as small steps, side steps, and backward walking that existing methods can hardly detect. This approach is also more robust in critical situations, when for example the wearer is sitting and moving the ankle or when the wearer is bicycling (less than two false detected strides per hour on average). As a consequence, the algorithm proposed for trajectory reconstruction achieves much better performances than existing methods for daily life contexts, in particular in narrow areas such as in a house. The computed stride trajectory contains essential information for recognizing the activity (atypical stride, walking, running, and stairs). For this task, we adopt a machine learning approach based on descriptors of these trajectories, which is shown to be robust to a large of variety of gaits. We tested our algorithm on recordings of healthy adults and children, achieving more than 99% success. The algorithm also achieved more than 97% success in challenging situations recorded by children suffering from movement disorders. Compared to most algorithms in the literature, this original method does not use a fixed-size sliding window but infers this last in an adaptive way.