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Hamdi, M.

Publications and source records attributed to Hamdi, M..

3 recordsLinked to original sources

DeepLUAD: An efficient approach for lung adenocarcinoma pattern classification

Histopathological analysis of whole-slide images is the gold standard technique for diagnosis of lung cancer and classifying it into types and subtypes by specialized pathologists. This labor-based approach is time and effort consuming, which led to development of automatic approaches to assist in reducing the time and effort. Deep learning is a supervised classification approach that is well adapted for automatic classification of histopathological images. We aimed to develop a deep learning-based approach for lung adenocarcinoma pattern classification and generalize the proposed approach to the classification of the major non-small cell lung cancer types. Three publicly available datasets were used in this study. A deep learning approach for histopathological image analysis using convolutional neural networks was developed and incorporated into automatic pipelines to accurately classify the predominant patterns on the whole-slide images level and non-small cell lung cancer types on patch-level. The models were evaluated using the confusion matrix to perform an error analysis and the classification report to compute F1-score, recall and precision. As results, the three models have shown an excellent performance with best combination of hyper-parameters for training models. First and second models predicted adenocarcinoma predominant patterns on two different datasets with an accuracy, respectively, of 96.15% and 89.51%. The third model has exceeded an accuracy of 99.72% in classifying major non-small cell lung cancer types. The proposed deep learning-based lung cancer classification approach can be used to assist pathologists in identifying of lung adenocarcinomas patterns.

bioinformatics↗

In silico screening of TMPRSS2 SNPs that affect its binding with SARS-CoV2 spike protein and directly involved in the interaction affinity changes

In this paper, we used in silico analysis to shed light on the possible interaction between TMPRSS2 and SARS-CoV2 spike (S) protein by examining the role of TMPRSS2 single nucleotide polymorphisms (SNPs) in relation with susceptibility and inter-individual variability of SARS-CoV2 infection. First, we used molecular docking of human TMPRSS2 protein to predict the binding site of TMPRSS2, especially the TMPRSS2 link loops, in order to assess the effect TMPRSS2 SNPs. The latter lead to missense variants on the interaction between TMPRSS2 and SARS-CoV2 S protein. In a second step, we further refine our analysis by performing a structure-function analysis of the complexes using PyMol software, and finally by MD simulations to validate the as-obtained results. Our findings show that 17 SNPs among the 692 natural TMPRSS2 coding variants are in positions to influence the binding of TMPRSS2 with the viral S protein. All of them give more important interaction energy as assessed by docking. Among the 17 SNPs, four missense variants E389A, K392Q, T393S and Q438E lead to "directly increasing" the interaction affinity and 2 missense variants R470I and Y416C cause it "directly decreasing". The R470I and Y416C present in African and American population, respectively. While the other 4 SNP variants (E389A; K392Q; T393S and Q438E) are present only in the European population, which could link the viral infection susceptibility to demographic, geographic and genetic factors.

bioinformatics↗

An immature subset of neuroblastoma cells synthesizes retinoic acid and depends on this metabolite

Neuroblastoma is a pediatric tumor of the adrenergic sympathetic lineage. Most high risk neuroblastoma go in complete clinical remission by chemotherapy, which is subsequently complemented by retinoic acid (RA) maintenance therapy. However, by unresolved mechanisms most tumors ultimately relapse as therapy-resistant disease. Neuroblastoma cell lines were recently found to include, besides lineage committed adrenergic (ADRN) tumor cells, also immature mesenchymal (MES) tumor cells. Here, we report that MES-type cells synthesize RA and require this metabolite for proliferation and motility. MES cells are even resistant to RA in vitro. MES cells appear to resemble Schwann Cell Precursors (SCP), which are motile precursors of the adrenergic lineage. MES and SCP cells express shared RA-synthesis and RA-target genes. Endogenous RA synthesis and RA resistance thus stem from normal programs of lineage precursors that are maintained in an immature tumor cell fraction. These cells are fully malignant in orthotopic patient-derived xenograft models and may mediate development of drug-resistant relapses.

cancer biology↗