Motivation: Spatial transcriptomics enables the analysis of cell crosstalk in healthy and diseased organs by capturing the transcriptomic profiles of millions of cells within their spatial contexts. However, spatial transcriptomics approaches also raise new computational challenges for the multidimensional data analysis associated with spatial coordinates.
Results: In this context, we introduce a novel analytical framework called CellsFromSpace based on independent component analysis (ICA), which allows users to analyze various commercially available technologies without relying on a single-cell reference dataset.
Nat Commun
February 2024
Introduction: Serum prostate specific antigen (PSA) is a well-known prognostic parameter in men with prostate cancer. The treatment of men with very high PSA values and apparently no detectable metastases is not fully established.
Patients And Methods: Ancillary analysis from the GETUG 12 phase 3 trial.
Triple-negative breast cancer (TNBC) is a rare cancer, characterized by high metastatic potential and poor prognosis, and has limited treatment options. The current standard of care in nonmetastatic settings is neoadjuvant chemotherapy (NACT), but treatment efficacy varies substantially across patients. This heterogeneity is still poorly understood, partly due to the paucity of curated TNBC data.
View Article and Find Full Text PDFJ Bioinform Comput Biol
October 2022
The development of prognostic molecular signatures considering the inter-patient heterogeneity is a key challenge for the precision medicine. We propose a joint model of this heterogeneity and the patient survival, assuming that tumor expression results from a mixture of a subset of independent signatures. We deconvolute the omics data using a non-parametric independent component analysis with a double sparseness structure for the source and the weight matrices, corresponding to the gene-component and individual-component associations, respectively.
View Article and Find Full Text PDFIdentifying individual mechanisms involved in complex diseases, such as cancer, is essential for precision medicine. Their characterization is particularly challenging due to the unknown relationships of high-dimensional omics data and their inter-patient heterogeneity. We propose to model individual gene expression as a combination of unobserved molecular mechanisms (molecular components) that may differ between the individuals.
View Article and Find Full Text PDFBackground: Severe COVID-19 is associated with a high circulating level of calprotectin, the S100A8/S100A9 alarmin heterodimer. Baseline calprotectin amount measured in peripheral blood at diagnosis correlates with disease severity. The optimal use of this biomarker along COVID-19 course remains to be delineated.
View Article and Find Full Text PDFAside from PD-L1 expression, biomarkers of response to immune checkpoint inhibitors (ICIs) in non-small-cell lung cancer (NSCLC) are needed. In a previous retrospective analysis, we documented that fecal Akkermansia muciniphila (Akk) was associated with clinical benefit of ICI in patients with NSCLC or kidney cancer. In the current study, we performed shotgun-metagenomics-based microbiome profiling in a large cohort of patients with advanced NSCLC (n = 338) treated with first- or second-line ICIs to prospectively validate the predictive value of fecal Akk.
View Article and Find Full Text PDFUnlabelled: The outcomes of adolescents/young adults with osteosarcoma have not improved in decades. The chaotic karyotype of this rare tumor has precluded the identification of prognostic biomarkers and patient stratification. We reasoned that transcriptomic studies should overcome this genetic complexity.
View Article and Find Full Text PDFThe importance of integrating biomarkers into the TNM staging has been emphasized in the 8 Edition of the American Joint Committee on Cancer (AJCC) Staging system. In a pooled analysis of 2148 TNBC-patients in the adjuvant setting, TILs are found to strongly up and downstage traditional pathological-staging in the Pathological and Clinical Prognostic Stage Groups from the AJJC 8 edition Cancer Staging System. This suggest that clinical and research studies on TNBC should take TILs into account in addition to stage, as for example patients with stage II TNBC and high TILs have a better outcome than patients with stage I and low TILs.
View Article and Find Full Text PDFBasal/squamous (Ba/Sq) subtype represents an intrinsic and robust group in the consensus molecular classification of muscle-invasive bladder cancer (MIBC), with poor outcome and controversial chemosensitivity. We aimed to investigate the spectrum of intratumor heterogeneity (ITH) in the Ba/Sq subtype. First, we validated a 29-gene NanoString CodeSet to predict the Ba/Sq subtype for FFPE samples.
View Article and Find Full Text PDFObjective: Health risk behaviors (HRB) of childhood cancer survivors (CCS) are generally studied separately, despite the evidence suggesting that HRB are not independent. To our knowledge, few studies have examined HRB profiles in the former pediatric cancer patients. In this study, we identified HRB profiles and examined predictors engaging in unhealthy behaviors in CCS.
View Article and Find Full Text PDFFetal and neonatal alloimmune thrombocytopenia (FNAIT) is the consequence of platelet destruction by maternal alloantibodies against fetal human platelet antigens (HPA). This may result in intracranial haemorrhages (ICH) or even fetal death. Currently, fetal HPA genotyping is performed using invasive procedures.
View Article and Find Full Text PDFBackground: Data generated by phase I trials is richer than the classical binary DLT measured at the first cycle used as primary endpoints. Several works developed designs for more informative endpoints, e.g.
View Article and Find Full Text PDFPurpose: The aim of the current study was to conduct a pooled analysis of studies that have investigated the prognostic value of tumor-infiltrating lymphocytes (TILs) in early-stage triple negative breast cancer (TNBC).
Methods: Participating studies had evaluated the percentage infiltration of stromally located TILs (sTILs) that were quantified in the same manner in patient diagnostic samples of early-stage TNBC treated with anthracycline-based chemotherapy with or without taxanes. Cox proportional hazards regression models stratified by trial were used for invasive disease-free survival (iDFS; primary end point), distant disease-free survival (D-DFS), and overall survival (OS), fitting sTILs as a continuous variable adjusted for clinicopathologic factors.
Motivation: Detailed knowledge of coding sequences has led to different candidate models for pathogenic variant prioritization. Several deleteriousness scores have been proposed for the non-coding part of the genome, but no large-scale comparison has been realized to date to assess their performance.
Results: We compared the leading scoring tools (CADD, FATHMM-MKL, Funseq2 and GWAVA) and some recent competitors (DANN, SNP and SOM scores) for their ability to discriminate assumed pathogenic variants from assumed benign variants (using the ClinVar, COSMIC and 1000 genomes project databases).
Background: LY2780301, a dual inhibitor of protein kinase B (AKT) and the downstream effector p70 ribosomal protein S6 kinase (p70S6K), may inhibit progression in tumours relying on phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signalling pathway activation. This phase IB trial investigated the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), safety, pharmacokinetics (PK) and antitumour activity of LY2780301 plus gemcitabine in patients with advanced/metastatic solid tumours.
Methods: This was a non-randomised, open-label, dose escalation and dose expansion trial.
The most commonly used method for dose finding, the 3 + 3, has poor performance. New adaptive designs are more efficient. Nevertheless, they have reached a maximum performance level, and further improvement requires either larger sample sizes or outcomes measures richer than the simplistic severe toxicity measured at cycle 1.
View Article and Find Full Text PDFWe address here the issue of prioritizing non-coding mutations in the tumoral genome. To this aim, we created two independent computational models. The first (germline) model estimates purifying selection based on population SNP data.
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