Committee Chair

Qin, Hong

Committee Member

Sartipi, Mina; Wu, Dalei; Yang, Li

Department

Dept. of Computational Science

College

College of Engineering and Computer Science

Publisher

University of Tennessee at Chattanooga

Place of Publication

Chattanooga (Tenn.)

Abstract

High-throughput microfluidics-based assays can potentially increase the speed and quality of yeast replicative lifespan measurements that are related to aging. One major challenge is to efficiently convert large volumes of time-lapse images into quantitative measurements of yeast cell lifespan measurements. To address these issues, we developed several deep learning methods to analyze a large number of images collected from microfluidic experiments. First, we compared three deep learning architectures to classify microfluidic time-lapse images of dividing yeast cells into categories that represent different stages in the yeast replicative aging process. Second, we evaluated convolutional neural networks for detecting cells from microfluidic images. The YOLO and Mask R-CNN are trained with yeast microfluidic images and tested for object detection, and features extraction. The results indicate that YOLO had better performance in terms of object detection and accuracy. In contrast, the Mask R-CNN had better performance in terms of cell area and better detection when the number of cells inside the trap is less than 3 cells. Third, prototyping an algorithm that can evaluate cell division events through family trees of cells. We generated a null distribution using single cells inside microfluidic traps. Based on this null distribution, we prototyped a likelihood algorithm for cell tracking between images at different time-points. We inferred cell family trees through a trace-back method. The replicative lifespan of a mother cell can be counted as the number of bifurcating branches of its family tree. Linear regression showed that predictions of our prototype correlated with experimental observations. Forth, since it is challenging to visualize and interpret the time-series data gathered through time-lapse microscopy images, we have developed a circular plotting software tool, mPolar, to visualize the trends and patterns of the cell movements, and cell division events in a time-series. Overall, our methods have the potential to accelerate the efficiency and expand the range of quantitative measurement of yeast replicative aging experiments. This work lays a useful framework for sophisticated deep-learning processing of microfluidic-based assays of yeast replicative aging.

Acknowledgments

I would like to express the utmost gratitude to my advisor Dr. Hong Qin who has been a mentor and guide on this journey. His perceptive advice, support, keen analysis, and constant encouragement helped me see this project to a conclusion. I would like to thank Ms. Kim Sapp for her support and assistance. I also would like thank to Cody Whitt for his help with graph analysis and cloud platform. Last but not the least, thank you to my family and friends for their encouragement and help throughout this process. The work is partially supported by NSF CAREER award1453078 (transferred to 1720215), NSF award 1761839, a start-up fund, internal awards from the University of Tennessee at Chattanooga (Tennessee of Higher Education funds via the Center of Excellence in Applied Computational Science and Engineering), and the computing facility of the SimcCenter at the University of Tennessee at Chattanooga.

Degree

Ph. D.; A dissertation submitted to the faculty of the University of Tennessee at Chattanooga in partial fulfillment of the requirements of the degree of Doctor of Philosophy.

Date

12-2021

Subject

Machine learning; Microfluidics; Yeast

Keyword

Aging; classification; lifespan; object detection; visualization; yeast cell

Document Type

Doctoral dissertations

DCMI Type

Text

Extent

xx, 108 leaves

Language

English

Rights

http://rightsstatements.org/vocab/InC/1.0/

License

http://creativecommons.org/licenses/by/4.0/

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