Neutrophil-Mediated Tumor-Targeting Delivery System of Oncolytic Bacteria Combined with ICB for Melanoma Lung Metastasis Therapy.

Oncolytic bacteria are the most promising tumor target vector. Questions also remain regarding finding a balance between the therapeutic efficacy and safety of oncolytic bacteria. The critical measure of how this balance is maintained is the improvement in tumor colonization. Attenuated Salmonella typhimurium (VNP20009) as the only Salmonella strain to be evaluated in a clinical trial is a potential tumor therapeutic bacterium. A delivery system with controlled release of VNP after being loaded into neutrophils, which significantly increases the tumor-targeting of VNP and enhances its therapeutic efficacy in a melanoma lung metastasis model is constructed. To improve the synergistic therapeutic effect, a PD1 nanobody is applied to this system (NE(PD1nb)). NE(PD1nb) activate dendritic cells (DCs) differentiation and stimulate the M1-like differentiation of macrophages, and induce CD4+ T-cells maturity and cytotoxic CD8+ T-cells activation through DCs tumor antigen presentation.

The classification of stages of epiretinal membrane using convolutional neural network on optical coherence tomography image.

BACKGROUND AND OBJECTIVE: The gold standard for diagnosing epiretinal membranes is to observe the surface of the internal limiting membrane on optical coherence tomography images. The stages of the epiretinal membrane are used to decide the condition of the health of the membrane. The stages are not detected because some of them are similar. To accurately classify the stages, a deep-learning technology can be used to improve the classification accuracy. METHODS: A combinatorial fusion with multiple convolutional neural networks (CNN) algorithms are proposed to enhance the accuracy of a single image classification model. The proposed method was trained using a dataset of 1947 optical coherence tomography images diagnosed with the epiretinal membrane at the Taichung Veterans General Hospital in Taiwan. The images consisted of 4 stages; stages 1, 2, 3, and 4. RESULTS: The overall accuracy of the classification was 84%. The combination of five and six CNN models achieves the highest testing accuracy (85%) among other combinations, respectively. Any combination with a different number of CNN models outperforms any single CNN algorithm working alone. Meanwhile, the accuracy of the proposed method is better than ophthalmologists with years of clinical experience. CONCLUSIONS: We have developed an efficient epiretinal membrane classification method by using combinatorial fusion with CNN models on optical coherence tomography images. The proposed method can be used for screening purposes to facilitate ophthalmologists making the correct diagnoses in general medical practice.

AVATAR: a database for genome-wide alternative splicing event detection using large scale ESTs and mRNAs.

UNLABELLED: In the past years, identification of alternative splicing (AS) variants has been gaining momentum. We developed AVATAR, a database for documenting AS using 5,469,433 human EST sequences and 26,159 human mRNA sequences. AVATAR contains 12000 alternative splicing sites identified by mapping ESTs and mRNAs with the whole human genome sequence. AVATAR also contains AS information for 6 eukaryotes. We mapped EST alignment information into a graph model where exons and introns are represented with vertices and edges, respectively. AVATAR can be queried using, (1) gene names, (2) number of identified AS events in a gene, (3) minimal number of ESTs supporting a splicing site, etc. as search parameters. The system provides visualized AS information for queried genes. AVAILABILITY: The database is available for free at http://avatar.iecs.fcu.edu.tw/

MuSiC: a tool for multiple sequence alignment with constraints.

SUMMARY: MuSiC is a web server to perform the constrained alignment of a set of sequences, such that the user-specified residues/nucleotides are aligned with each other. The input of the MuSiC system consists of a set of protein/DNA/RNA sequences and a set of user-specified constraints, each with a fragment of residue/nucleotide that (approximately) appears in all input sequences. The output of MuSiC is a constrained multiple sequence alignment in which the fragments of the input sequences whose residues/nucleotides exhibit a given degree of similarity to a constraint are aligned together. The current MuSiC system is implemented in Java language and can be accessed via a simple web interface. AVAILABILITY: http://genome.life.nctu.edu.tw/MUSIC

Constrained multiple sequence alignment tool development and its application to RNase family alignment.

In this paper, we design a heuristic algorithm of computing a constrained multiple sequence alignment (CMSA for short) for guaranteeing that the generated alignment satisfies the user-specified constraints that some particular residues should be aligned together. If the number of residues needed to be aligned together is a constant alpha, then the time-complexity of our CMSA algorithm for aligning K sequences is O(alphaKn(4)), where n is the maximum of the lengths of sequences. In addition, we have built up such a CMSA software system and made several experiments on the RNase sequences, which mainly function in catalyzing the degradation of RNA molecules. The resulting alignments illustrate the practicability of our method.

Constrained multiple sequence alignment tool development and its application to RNase family alignment.

In this paper, we design an algorithm of computing a constrained multiple sequence alignment (CMSA for short) for guaranteeing that the generated alignment satisfies the user-specified constraints that some particular residues should be aligned together. If the number of residues needed to be aligned together is a constant alpha, then the time-complexity of our CMSA algorithm for aligning K sequences is O (alphaKn4), where n is the maximum of the lengths of sequences. In addition, we have build up such a CMSA software system and made several experiments on the RNase sequences, which mainly function in catalyzing the degradation of RNA molecules. The resulting alignments illustrate the practicability of our method.