Biology subjects

Matsuoka, Y.

Publications and source records attributed to Matsuoka, Y..

4 recordsLinked to original sources

bioRxiv2018

Automatic Single-Cell Discrimination by Cellular Appearance using Convolutional Neural Network

Morphological images of cells contain extensive information, which help biologists to infer the type and state of cells to some degree based on their morphology. Convolutional Neural Network, a neural network architecture, is a powerful tool used for image recognition. However, whether it can be used to classify cells on the basis of their morphology remains unclear. In this study, we demonstrate that 10 different hematopoietic tumor cell lines with similar morphologies that biologists find difficult to distinguish can be classified with >90% accuracy using only their bright-field images when analyzed using a Convolutional Neural Network. This novel and simple system using bright-field images of cells could be a powerful analytical tool for cell type discrimination and could also be applied to the clinical diagnoses of hematopoietic tumors.

cell biology↗

bioRxiv2018

Network-guided Discovery of Influenza Virus Replication Host Factors

The position of host factors required for viral replication within a human protein-protein interaction (PPI) network can be exploited to identify drug targets that are robust to drug-mediated selective pressure. Host factors can physically interact with viral proteins, be a component of pathways regulated by viruses (where proteins themselves do not interact with viral proteins) or be required for viral replication but unregulated by viruses. Here, we demonstrate a method of combining a human PPI network with virus-host protein interaction data to improve antiviral drug discovery for influenza viruses by identifying target host proteins. Network analysis shows that influenza virus proteins physically interact with host proteins in network positions significant for information flow. We have isolated a subnetwork of the human PPI network which connects virus-interacting host proteins to host factors that are important for influenza virus replication without physically interacting with viral proteins. The subnetwork is enriched for signaling and immune processes. Selecting proteins based on network topology within the subnetwork, we performed an siRNA screen to determine if the subnetwork was enriched for virus replication host factors and if network position within the subnetwork offers an advantage in prioritization of drug targets to control influenza virus replication. We found that the subnetwork is highly enriched for target host proteins - more so than the set of host factors that physically interact with viral proteins. Our findings demonstrate that network positions are a powerful predictor to guide antiviral drug candidate prioritization.\n\nIMPORTANCEIntegrating virus-host interactions with host protein-protein interactions, we have created a method using these established network practices to identify host factors (i.e. proteins) that are likely candidates for antiviral drug targeting. We demonstrate that interaction cascades between host proteins that directly interact with viral proteins and host factors that are important to influenza replication are enriched for signaling and immune processes. Additionally, we show that host proteins that interact with viral proteins are in network locations of power. Finally, we demonstrate a new network methodology to predict novel host factors and validate predictions with an siRNA screen. Our results show that integrating virus-host proteins interactions is useful in the identification of antiviral drug target candidates.

systems biology↗

bioRxiv2017

Melanin pathway genes regulate color and morphology of butterfly wing scales

The cuticular skeleton of a butterfly wing scale cell serves both as a substrate for the deposition of pigments and as an exquisitely finely-sculpted material responsible for the production of structural colors. While cuticle rigidity and pigmentation depend to a large extent on the end products of a branched biochemical pathway - the melanin pathway - little is known whether genes in this pathway also play a role in the development of specific scale morphologies that might aid in the development of structural colors. Here we first show that male and female Bicyclus anynana butterflies display differences in scale size and scale morphology but no differences in scale color. Then we use CRISPR/Cas9 to show that knockout mutations in five genes that function in the melanin pathway, TH, DDC, yellow, ebony, and aaNAT, affect both the fine structure and the coloration of the wing scales. Most dramatically, mutations in yellow led to extra horizontal cuticular laminae on the surface of scales, whereas mutations in DDC led to taller and sheet-like vertical cuticular laminae throughout each scale. We identify some of the first genes affecting the development of scale morphology, and whose regulation and pleiotropic effects may be important in creating, as well as limiting, the diversity of structural as well as pigmentary colors observed in butterflies.

genetics↗

bioRxiv2017

Genetic basis of melanin pigmentation in butterfly wings

Despite the variety, prominence, and adaptive significance of butterfly wing patterns surprisingly little known about the genetic basis of wing color diversity. Even though there is intense interest in wing pattern evolution and development, the technical challenge of genetically manipulating butterflies has slowed efforts to functionally characterize color pattern development genes. To identify candidate wing pigmentation genes we used RNA-seq to characterize transcription across multiple stages of butterfly wing development, and between different color pattern elements, in the painted lady butterfly Vanessa cardui. This allowed us to pinpoint genes specifically associated with red and black pigment patterns. To test the functions of a subset of genes associated with presumptive melanin pigmentation we used CRISPR/Cas9 genome editing in four different butterfly genera. pale, Ddc, and yellow knockouts displayed reduction of melanin pigmentation, consistent with previous findings in other insects. Interestingly, however, yellow-d, ebony, and black knockouts revealed that these genes have localized effects on tuning the color of red, brown, and ochre pattern elements. These results point to previously undescribed mechanisms for modulating the color of specific wing pattern elements in butterflies, and provide an expanded portrait of the insect melanin pathway.

genetics↗