Digging deep into Golgi phenotypic diversity with unsupervised machine learning

The synthesis of glycans and the sorting of proteins are critical functions of the Golgi apparatus and depend on its highly complex and compartmentalized architecture. High-content image analysis coupled to RNA interference screening offers opportunities to explore this organelle organization and th...

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Main Authors: Wang, Yi, Huang, Dong, Bard, Frederic, Ke, Yiping, Lee, Kee Khoon, Hussain, Shaista, Le Guezennec, Xavier, Chia, Joanne
Other Authors: Sommer, Thomas
Format: Journal Article
Language:English
Published: 2018
Subjects:
Online Access:https://hdl.handle.net/10356/102613
http://hdl.handle.net/10220/47249
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author Wang, Yi
Huang, Dong
Bard, Frederic
Ke, Yiping
Lee, Kee Khoon
Hussain, Shaista
Le Guezennec, Xavier
Chia, Joanne
author2 Sommer, Thomas
author_facet Sommer, Thomas
Wang, Yi
Huang, Dong
Bard, Frederic
Ke, Yiping
Lee, Kee Khoon
Hussain, Shaista
Le Guezennec, Xavier
Chia, Joanne
author_sort Wang, Yi
collection NTU
description The synthesis of glycans and the sorting of proteins are critical functions of the Golgi apparatus and depend on its highly complex and compartmentalized architecture. High-content image analysis coupled to RNA interference screening offers opportunities to explore this organelle organization and the gene network underlying it. To date, image-based Golgi screens have based on a single parameter or supervised analysis with predefined Golgi structural classes. Here, we report the use of multiparametric data extracted from a single marker and a computational unsupervised analysis framework to explore Golgi phenotypic diversity more extensively. In contrast with the three visually definable phenotypes, our framework reproducibly identified 10 Golgi phenotypes. They were used to quantify and stratify phenotypic similarities among genetic perturbations. The derived phenotypic network partially overlaps previously reported protein–protein interactions as well as suggesting novel functional interactions. Our workflow suggests the existence of multiple stable Golgi organizational states and provides a proof of concept for the classification of drugs and genes using fine-grained phenotypic information.
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spelling ntu-10356/1026132020-03-07T11:50:48Z Digging deep into Golgi phenotypic diversity with unsupervised machine learning Wang, Yi Huang, Dong Bard, Frederic Ke, Yiping Lee, Kee Khoon Hussain, Shaista Le Guezennec, Xavier Chia, Joanne Sommer, Thomas School of Computer Science and Engineering Golgi Phenotypic Diversity DRNTU::Science::Biological sciences The synthesis of glycans and the sorting of proteins are critical functions of the Golgi apparatus and depend on its highly complex and compartmentalized architecture. High-content image analysis coupled to RNA interference screening offers opportunities to explore this organelle organization and the gene network underlying it. To date, image-based Golgi screens have based on a single parameter or supervised analysis with predefined Golgi structural classes. Here, we report the use of multiparametric data extracted from a single marker and a computational unsupervised analysis framework to explore Golgi phenotypic diversity more extensively. In contrast with the three visually definable phenotypes, our framework reproducibly identified 10 Golgi phenotypes. They were used to quantify and stratify phenotypic similarities among genetic perturbations. The derived phenotypic network partially overlaps previously reported protein–protein interactions as well as suggesting novel functional interactions. Our workflow suggests the existence of multiple stable Golgi organizational states and provides a proof of concept for the classification of drugs and genes using fine-grained phenotypic information. Published version 2018-12-27T06:36:03Z 2019-12-06T20:57:35Z 2018-12-27T06:36:03Z 2019-12-06T20:57:35Z 2017 Journal Article Hussain, S., Le Guezennec, X., Wang, Y., Huang, D., Chia, J., Ke, Y., . . . Bard, F. (2017). Digging deep into Golgi phenotypic diversity with unsupervised machine learning. Molecular Biology of the Cell, 28(25), 3686-3698. doi: 10.1091/mbc.e17-06-0379 1059-1524 https://hdl.handle.net/10356/102613 http://hdl.handle.net/10220/47249 10.1091/mbc.e17-06-0379 en Molecular Biology of the Cell © 2017 Hussain, Le Guezennec, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). 13 p. application/pdf
spellingShingle Golgi
Phenotypic Diversity
DRNTU::Science::Biological sciences
Wang, Yi
Huang, Dong
Bard, Frederic
Ke, Yiping
Lee, Kee Khoon
Hussain, Shaista
Le Guezennec, Xavier
Chia, Joanne
Digging deep into Golgi phenotypic diversity with unsupervised machine learning
title Digging deep into Golgi phenotypic diversity with unsupervised machine learning
title_full Digging deep into Golgi phenotypic diversity with unsupervised machine learning
title_fullStr Digging deep into Golgi phenotypic diversity with unsupervised machine learning
title_full_unstemmed Digging deep into Golgi phenotypic diversity with unsupervised machine learning
title_short Digging deep into Golgi phenotypic diversity with unsupervised machine learning
title_sort digging deep into golgi phenotypic diversity with unsupervised machine learning
topic Golgi
Phenotypic Diversity
DRNTU::Science::Biological sciences
url https://hdl.handle.net/10356/102613
http://hdl.handle.net/10220/47249
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