Search bioRxiv⌕ Search

Biology subjects

Rioux-Leclercq, N.

Publications and source records attributed to Rioux-Leclercq, N..

2 recordsLinked to original sources

A deep learning model trained on only eight whole-slide images accurately segments tumors: wise data use versus big data

Computer-assisted pathology is one of the biggest challenges in the medicine of the future. However, artificial intelligence is struggling to gain acceptance in the broader medical community due to data security issues, lack of trust in the machine, and poor data availability. Here, we develop a tumor delineation algorithm with only eight whole slide images of ovarian cancer to demonstrate the feasibility of an artificial intelligence application created from only a few data, finely annotated and with optimal processing. We test the model on seventeen other slides from the same hospital. The predictions are similar to the ground truth annotations made by an expert pathologist, with a mean DICE score of 0.90 [0.85 - 0.93]. The results on slides from another hospital are consistent, suggesting that the model is generalizable and that its performance does not suffer from different data acquisition. This study demonstrates the feasibility of a contouring algorithm based on a reduced dataset well optimized, going against the commonly accepted idea that a phenomenal amount of data is paramount. This study paves the way for other medical applications, especially for rare pathologies with limited available data.

bioinformatics↗

Molecular basis for a novel systemic form of human hereditary apoA-I amyloidosis with vision loss

Hereditary apolipoprotein A-I (apoA-I) amyloidosis (AApoAI) is a life-threatening incurable genetic disorder whose molecular underpinnings and the full spectrum of afflicted organs are unclear. We report a new form of AApoAI with amyloid deposition in multiple organs, including an unprecedented retinal amyloidosis. Genetic and proteomic analyses identified Glu34Lys apoA-I as the fibrillar protein causing the clinical manifestations. A life-saving combined hepatorenal transplantation was performed for one Glu34Lys carrier. To elucidate structural underpinnings for amyloidogenic properties of Glu34Lys, we generated its recombinant globular domain and compared the conformation and dynamics of its lipid-free form with those of two other naturally occurring apoA-I variants, Phe71Tyr (amyloidogenic) and Leu159Arg (non-amyloidogenic). All variants showed reduced stability and altered aromatic residue packing. Molecular dynamics simulations revealed local helical unfolding and suggested that transient opening of Trp72 induced mutation-dependent structural perturbations in a sensitive region, including the major amyloid hotspot residues 14-22. We posit that a shift from the \"closed\" to an \"open\" orientation of Trp72 modulates structural protection of amyloid hotspots, suggesting a previously unknown early step in protein misfolding.

molecular biology↗