8,479 research outputs found
SVSBI: Sequence-based virtual screening of biomolecular interactions
Virtual screening (VS) is an essential technique for understanding
biomolecular interactions, particularly, drug design and discovery. The
best-performing VS models depend vitally on three-dimensional (3D) structures,
which are not available in general but can be obtained from molecular docking.
However, current docking accuracy is relatively low, rendering unreliable VS
models. We introduce sequence-based virtual screening (SVS) as a new generation
of VS models for modeling biomolecular interactions. The SVS model utilizes
advanced natural language processing (NLP) algorithms and optimizes deep
-embedding strategies to encode biomolecular interactions without invoking
3D structure-based docking. We demonstrate the state-of-art performance of SVS
for four regression datasets involving protein-ligand binding, protein-protein,
protein-nucleic acid binding, and ligand inhibition of protein-protein
interactions and five classification datasets for the protein-protein
interactions in five biological species. SVS has the potential to dramatically
change the current practice in drug discovery and protein engineering
The Expression Levels of XLF and Mutant P53 Are Inversely Correlated in Head and Neck Cancer Cells.
XRCC4-like factor (XLF), also known as Cernunnos, is a protein encoded by the human NHEJ1 gene and an important repair factor for DNA double-strand breaks. In this study, we have found that XLF is over-expressed in HPV(+) versus HPV(-) head and neck squamous cell carcinoma (HNSCC) and significantly down-regulated in the HNSCC cell lines expressing high level of mutant p53 protein versus those cell lines harboring wild-type TP53 gene with low p53 protein expression. We have also demonstrated that Werner syndrome protein (WRN), a member of the NHEJ repair pathway, binds to both mutant p53 protein and NHEJ1 gene promoter, and siRNA knockdown of WRN leads to the inhibition of XLF expression in the HNSCC cells. Collectively, these findings suggest that WRN and p53 are involved in the regulation of XLF expression and the activity of WRN might be affected by mutant p53 protein in the HNSCC cells with aberrant TP53 gene mutations, due to the interaction of mutant p53 with WRN. As a result, the expression of XLF in these cancer cells is significantly suppressed. Our study also suggests that XLF is over-expressed in HPV(+) HNSCC with low expression of wild type p53, and might serve as a potential biomarker for HPV(+) HNSCC. Further studies are warranted to investigate the mechanisms underlying the interactive role of WRN and XLF in NHEJ repair pathway
Reversible Recursive Instance-level Object Segmentation
In this work, we propose a novel Reversible Recursive Instance-level Object
Segmentation (R2-IOS) framework to address the challenging instance-level
object segmentation task. R2-IOS consists of a reversible proposal refinement
sub-network that predicts bounding box offsets for refining the object proposal
locations, and an instance-level segmentation sub-network that generates the
foreground mask of the dominant object instance in each proposal. By being
recursive, R2-IOS iteratively optimizes the two sub-networks during joint
training, in which the refined object proposals and improved segmentation
predictions are alternately fed into each other to progressively increase the
network capabilities. By being reversible, the proposal refinement sub-network
adaptively determines an optimal number of refinement iterations required for
each proposal during both training and testing. Furthermore, to handle multiple
overlapped instances within a proposal, an instance-aware denoising autoencoder
is introduced into the segmentation sub-network to distinguish the dominant
object from other distracting instances. Extensive experiments on the
challenging PASCAL VOC 2012 benchmark well demonstrate the superiority of
R2-IOS over other state-of-the-art methods. In particular, the
over classes at IoU achieves , which significantly
outperforms the results of by PFN~\cite{PFN} and
by~\cite{liu2015multi}.Comment: 9 page
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