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Mapping and annotating the mammalian body-wide protein-coding gene expression

Time: Fri 2022-06-03 09.30

Location: Eva & Georg Klein, Biomedicum, Solnavägen 9, Solna

Video link: https://kth-se.zoom.us/j/66922122998

Language: English

Subject area: Biotechnology

Doctoral student: Max Karlsson , Science for Life Laboratory, SciLifeLab, Systembiologi, Integrative omics and precision medicine

Opponent: Professor Julio Saez-Rodriguez, Faculty of Medicine, Heidelberg University, Heidelberg, Germany

Supervisor: Professor Mathias Uhlén, Science for Life Laboratory, SciLifeLab, Albanova VinnExcellence Center for Protein Technology, ProNova, Systembiologi; Doktor Linn Fagerberg, Proteinvetenskap, Science for Life Laboratory, SciLifeLab

QC 2022-05-11

Abstract

A central aim of fundamental research is to create conditions necessary for fueling further research and innovation. Our understanding of basic biology is central for future developments of tools for diagnosing, monitoring, and treating disease. This doctoral thesis focuses on mapping the mammalian protein-coding gene expression in healthy cells and tissues, and annotation of genes based on their expression patterns, specificity, location, and function. This has in large part been achieved by using large scale transcriptomic and proteomic profiling to describe the gene expression landscape that defines the identities of the great diversity of cells present in mammals. Characterization of gene expression across different tissues and cell types provide fundamental tools to enable the exploration, summary, and ultimately, the annotation of the mammalian proteome, which is still incomplete.

The studies comprising this thesis have contributed to the Human Protein Atlas, an online open-access portal for proteomic and transcriptomic data, with the aim to profile each human protein-coding gene to create a spatial map of the molecular organization of the human body, providing basic tools for the scientific community. Paper I comprises an effort to catalogue all proteins that are actively secreted from cells; defining the human secretome. Paper II entails the deep characterization and annotation of the protein-coding transcriptome of 18 peripheral immune cell types. Paper III describes the, to date, most comprehensive tissue-based transcriptomic profiling of protein-coding genes in 98 tissues of the increasingly important model animal pig. Paper IV extends previous tissue-based maps of the human protein-coding genome by integration of 13 single cell transcriptome datasets. Paper V explores the human protein-coding genome in a clustering-based annotation of co-expressed genes across single cells and tissues to provide a framework for finding previously unknown functional relationships between genes by the principle of “guilt-by-association”.

In summary, the work described here entails a small contribution to the grand effort of spatially mapping proteins across tissues and cell types, for building a framework of biological knowledge that can lead to increased understanding of the constituents that make us humans.

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