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Biology subjects

Digre, A.

Publications and source records attributed to Digre, A..

2 recordsLinked to original sources

A high-resolution spatial map of cilia-associated proteins in the human fallopian tube

Molecular alterations in the fallopian tubes play a pivotal role in the development of cancer and reproductive disorders, yet their molecular landscape at the protein level remains poorly defined. Here, we map key fallopian tube proteins at single-cell resolution utilizing an integrated transcriptomics and proteomics approach. Based on RNA-seq analysis we identify 310 genes with elevated expression in fallopian tube, the majority of which are associated with motile cilia function. We spatially characterize 133 of the corresponding proteins in fallopian tube and other human tissues with motile cilia to subcellular structures of ciliated cells, validating the findings with single-cell RNA-seq and mass-spectrometry data. Eleven proteins previously only studied on the transcript level without information in cilia databases are further analyzed in a hydrosalpinx patient, showing a thinner epithelium, lower density of FOXJ1 expression, and reduced expression of FHAD1, RIIAD1, and C2orf81. Our high-resolution spatial map aids in dissecting the pathways underlaying infertility and diseases linked to cilia-specific functions.

molecular biology↗

Genome-wide single cell annotation of the human protein-coding genes

An important quest for the life science community is to deliver a complete annotation of the human building-blocks of life, the genes and the proteins. Here, we report on a genome-wide effort to annotate all protein-coding genes based on single cell transcriptomics data representing all major tissues and organs in the human body, integrated with data from bulk transcriptomics and antibody-based tissue profiling. Altogether, 25 tissues have been analyzed with single cell transcriptomics resulting in genome-wide expression in 444 single cell types using a strategy involving pooling data from individual cells to obtain genome-wide expression profiles of individual cell type. We introduce a new genome-wide classification tool based on clustering of similar expression profiles across single cell types, which can be visualized using dimensional reduction maps (UMAP). The clustering classification is integrated with a new "tau" score classification for all protein-coding genes, resulting in a measure of single cell specificity across all cell types for all individual genes. The analysis has allowed us to annotate all human protein-coding genes with regards to function and spatial distribution across individual cell types across all major tissues and organs in the human body. A new version of the open access Human Protein Atlas (www.proteinatlas.org) has been launched to enable researchers to explore the new genome-wide annotation on an individual gene level.

systems biology↗