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Article ; Online: Human pluripotent stem cell-based organoids and cell platforms for modelling SARS-CoV-2 infection and drug discovery.

Giani, Alice Maria / Chen, Shuibing

2021 Volume 53, Page(s) 102207

Abstract: The coronavirus disease 2019 (COVID-19) global pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected over 200 countries and territories worldwide and resulted in more than 2.5 million deaths. In a pressing ...

Abstract	The coronavirus disease 2019 (COVID-19) global pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected over 200 countries and territories worldwide and resulted in more than 2.5 million deaths. In a pressing search for treatments and vaccines, research models based on human stem cells are emerging as crucial tools to investigate SARS-CoV-2 infection mechanisms and cellular responses across different tissues. Here, we provide an overview of the variety of human pluripotent stem cell-based platforms adopted in SARS-CoV-2 research, comprising monolayer cultures and organoids, which model the multitude of affected tissues in vitro. We highlight the strengths of these platforms, including their application to assess both the susceptible cell types and the pathogenesis of SARS-CoV-2. We describe their use to identify drug candidates for further investigation in addition to discussing their limitations in fully recapitulating COVID-19 pathophysiology. Overall, stem cell models are facilitating the understanding of SARS-CoV-2 and prove to be versatile platforms for studying infections.
MeSH term(s)	COVID-19 ; Drug Discovery ; Humans ; Organoids ; Pluripotent Stem Cells ; SARS-CoV-2
Language	English
Publishing date	2021-02-20
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2393143-7
ISSN	1876-7753 ; 1873-5061
ISSN (online)	1876-7753
ISSN	1873-5061
DOI	10.1016/j.scr.2021.102207
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Long walk to genomics: History and current approaches to genome sequencing and assembly

Giani, Alice Maria / Gallo, Guido Roberto / Gianfranceschi, Luca / Formenti, Giulio

Computational and Structural Biotechnology Journal. 2020, v. 18

2020

Abstract: Genomes represent the starting point of genetic studies. Since the discovery of DNA structure, scientists have devoted great efforts to determine their sequence in an exact way. In this review we provide a comprehensive historical background of the ... ...

Abstract	Genomes represent the starting point of genetic studies. Since the discovery of DNA structure, scientists have devoted great efforts to determine their sequence in an exact way. In this review we provide a comprehensive historical background of the improvements in DNA sequencing technologies that have accompanied the major milestones in genome sequencing and assembly, ranging from early sequencing methods to Next-Generation Sequencing platforms. We then focus on the advantages and challenges of the current technologies and approaches, collectively known as Third Generation Sequencing. As these technical advancements have been accompanied by progress in analytical methods, we also review the bioinformatic tools currently employed in de novo genome assembly, as well as some applications of Third Generation Sequencing technologies and high-quality reference genomes.
Keywords	DNA ; analytical methods ; bioinformatics ; genome ; genome assembly ; genomics ; high-throughput nucleotide sequencing ; nucleotide sequences
Language	English
Size	p. 9-19.
Publishing place	Elsevier B.V.
Document type	Article
ISSN	2001-0370
DOI	10.1016/j.csbj.2019.11.002
Database	NAL-Catalogue (AGRICOLA)

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Article: Long walk to genomics: History and current approaches to genome sequencing and assembly.

Giani, Alice Maria / Gallo, Guido Roberto / Gianfranceschi, Luca / Formenti, Giulio

Computational and structural biotechnology journal

2019 Volume 18, Page(s) 9–19

Abstract	Genomes represent the starting point of genetic studies. Since the discovery of DNA structure, scientists have devoted great efforts to determine their sequence in an exact way. In this review we provide a comprehensive historical background of the improvements in DNA sequencing technologies that have accompanied the major milestones in genome sequencing and assembly, ranging from early sequencing methods to Next-Generation Sequencing platforms. We then focus on the advantages and challenges of the current technologies and approaches, collectively known as Third Generation Sequencing. As these technical advancements have been accompanied by progress in analytical methods, we also review the bioinformatic tools currently employed in
Language	English
Publishing date	2019-11-17
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2694435-2
ISSN	2001-0370
ISSN	2001-0370
DOI	10.1016/j.csbj.2019.11.002
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Human iPSC 4R tauopathy model uncovers modifiers of tau propagation.

Parra Bravo, Celeste / Giani, Alice Maria / Madero-Perez, Jesus / Zhao, Zeping / Wan, Yuansong / Samelson, Avi J / Wong, Man Ying / Evangelisti, Alessandro / Cordes, Ethan / Fan, Li / Ye, Pearly / Zhu, Daphne / Pozner, Tatyana / Mercedes, Maria / Patel, Tark / Yarahmady, Allan / Carling, Gillian K / Sterky, Fredrik H / Lee, Virginia M Y /

Lee, Edward B / DeTure, Michael / Dickson, Dennis W / Sharma, Manu / Mok, Sue-Ann / Luo, Wenjie / Zhao, Mingrui / Kampmann, Martin / Gong, Shiaoching / Gan, Li

Cell

2024 Volume 187, Issue 10, Page(s) 2446–2464.e22

Abstract: Tauopathies are age-associated neurodegenerative diseases whose mechanistic underpinnings remain elusive, partially due to a lack of appropriate human models. Here, we engineered human induced pluripotent stem cell (hiPSC)-derived neuronal lines to ... ...

Abstract	Tauopathies are age-associated neurodegenerative diseases whose mechanistic underpinnings remain elusive, partially due to a lack of appropriate human models. Here, we engineered human induced pluripotent stem cell (hiPSC)-derived neuronal lines to express 4R Tau and 4R Tau carrying the P301S MAPT mutation when differentiated into neurons. 4R-P301S neurons display progressive Tau inclusions upon seeding with Tau fibrils and recapitulate features of tauopathy phenotypes including shared transcriptomic signatures, autophagic body accumulation, and reduced neuronal activity. A CRISPRi screen of genes associated with Tau pathobiology identified over 500 genetic modifiers of seeding-induced Tau propagation, including retromer VPS29 and genes in the UFMylation cascade. In progressive supranuclear palsy (PSP) and Alzheimer's Disease (AD) brains, the UFMylation cascade is altered in neurofibrillary-tangle-bearing neurons. Inhibiting the UFMylation cascade in vitro and in vivo suppressed seeding-induced Tau propagation. This model provides a robust platform to identify novel therapeutic strategies for 4R tauopathy.
MeSH term(s)	Humans ; Induced Pluripotent Stem Cells/metabolism ; tau Proteins/metabolism ; Tauopathies/metabolism ; Tauopathies/pathology ; Neurons/metabolism ; Neurons/pathology ; Animals ; Mice ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Alzheimer Disease/genetics ; Brain/metabolism ; Brain/pathology ; Supranuclear Palsy, Progressive/metabolism ; Supranuclear Palsy, Progressive/pathology ; Supranuclear Palsy, Progressive/genetics ; Cell Differentiation ; Mutation ; Autophagy
Chemical Substances	tau Proteins ; MAPT protein, human
Language	English
Publishing date	2024-04-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2024.03.015
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Article ; Online: Isogenic human trophectoderm cells demonstrate the role of

iScience

2023 Volume 26, Issue 7, Page(s) 107001

Abstract: Population-based genome-wide association studies (GWAS) normally require a large sample size, which can be labor intensive and costly. Recently, we reported a human induced pluripotent stem cell (hiPSC) array-based GWAS method, identifying NDUFA4 as a ... ...

Abstract	Population-based genome-wide association studies (GWAS) normally require a large sample size, which can be labor intensive and costly. Recently, we reported a human induced pluripotent stem cell (hiPSC) array-based GWAS method, identifying NDUFA4 as a host factor for Zika virus (ZIKV) infection. In this study, we extended our analysis to trophectoderm cells, which constitute one of the major routes of mother-to-fetus transmission of ZIKV during pregnancy. We differentiated hiPSCs from various donors into trophectoderm cells. We then infected cells carrying loss of function mutations in
Language	English
Publishing date	2023-05-29
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.107001
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Article: Human iPSC 4R tauopathy model uncovers modifiers of tau propagation.

bioRxiv : the preprint server for biology

2023

Abstract: Tauopathies are age-associated neurodegenerative diseases whose mechanistic underpinnings remain elusive, partially due to lack of appropriate human models. Current human induced pluripotent stem cell (hiPSC)-derived neurons express very low levels of 4- ... ...

Abstract	Tauopathies are age-associated neurodegenerative diseases whose mechanistic underpinnings remain elusive, partially due to lack of appropriate human models. Current human induced pluripotent stem cell (hiPSC)-derived neurons express very low levels of 4-repeat (4R)-tau isoforms that are normally expressed in adult brain. Here, we engineered new iPSC lines to express 4R-tau and 4R-tau carrying the P301S
Language	English
Publishing date	2023-06-22
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.06.19.544278
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Scalable, accessible and reproducible reference genome assembly and evaluation in Galaxy.

Larivière, Delphine / Abueg, Linelle / Brajuka, Nadolina / Gallardo-Alba, Cristóbal / Grüning, Bjorn / Ko, Byung June / Ostrovsky, Alex / Palmada-Flores, Marc / Pickett, Brandon D / Rabbani, Keon / Antunes, Agostinho / Balacco, Jennifer R / Chaisson, Mark J P / Cheng, Haoyu / Collins, Joanna / Couture, Melanie / Denisova, Alexandra / Fedrigo, Olivier / Gallo, Guido Roberto /

Nature biotechnology

2024 Volume 42, Issue 3, Page(s) 367–370

MeSH term(s)	Computational Biology ; Software
Language	English
Publishing date	2024-01-24
Publishing country	United States
Document type	Letter
ZDB-ID	1311932-1
ISSN	1546-1696 ; 1087-0156
ISSN (online)	1546-1696
ISSN	1087-0156
DOI	10.1038/s41587-023-02100-3
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Zs.A 2167: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 137: Show issues
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Article ; Online: A human iPSC-array-based GWAS identifies a virus susceptibility locus in the NDUFA4 gene and functional variants.

Han, Yuling / Tan, Lei / Zhou, Ting / Yang, Liuliu / Carrau, Lucia / Lacko, Lauretta A / Saeed, Mohsan / Zhu, Jiajun / Zhao, Zeping / Nilsson-Payant, Benjamin E / Lira Neto, Filipe Tenorio / Cahir, Clare / Giani, Alice Maria / Chai, Jin Chou / Li, Yang / Dong, Xue / Moroziewicz, Dorota / Paull, Daniel / Zhang, Tuo /

Koo, Soyeon / Tan, Christina / Danziger, Ron / Ba, Qian / Feng, Lingling / Chen, Zhengming / Zhong, Aaron / Wise, Gilbert J / Xiang, Jenny Z / Wang, Hui / Schwartz, Robert E / tenOever, Benjamin R / Noggle, Scott A / Rice, Charles M / Qi, Qibin / Evans, Todd / Chen, Shuibing

Cell stem cell

2022 Volume 29, Issue 10, Page(s) 1475–1490.e6

Abstract: Population-based studies to identify disease-associated risk alleles typically require samples from a large number of individuals. Here, we report a human-induced pluripotent stem cell (hiPSC)-based screening strategy to link human genetics with viral ... ...

Abstract	Population-based studies to identify disease-associated risk alleles typically require samples from a large number of individuals. Here, we report a human-induced pluripotent stem cell (hiPSC)-based screening strategy to link human genetics with viral infectivity. A genome-wide association study (GWAS) identified a cluster of single-nucleotide polymorphisms (SNPs) in a cis-regulatory region of the NDUFA4 gene, which was associated with susceptibility to Zika virus (ZIKV) infection. Loss of NDUFA4 led to decreased sensitivity to ZIKV, dengue virus, and SARS-CoV-2 infection. Isogenic hiPSC lines carrying non-risk alleles of SNPs or deletion of the cis-regulatory region lower sensitivity to viral infection. Mechanistic studies indicated that loss/reduction of NDUFA4 causes mitochondrial stress, which leads to the leakage of mtDNA and thereby upregulation of type I interferon signaling. This study provides proof-of-principle for the application of iPSC arrays in GWAS and identifies NDUFA4 as a previously unknown susceptibility locus for viral infection.
MeSH term(s)	Humans ; Alleles ; COVID-19/genetics ; DNA, Mitochondrial/metabolism ; Electron Transport Complex IV/genetics ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Induced Pluripotent Stem Cells/metabolism ; Interferon Type I/metabolism ; Polymorphism, Single Nucleotide ; SARS-CoV-2 ; Zika Virus ; Zika Virus Infection/genetics ; Dengue/genetics
Chemical Substances	DNA, Mitochondrial ; Electron Transport Complex IV (EC 1.9.3.1) ; Interferon Type I ; NDUFA4 protein, human (EC 1.9.3.1)
Language	English
Publishing date	2022-10-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2375354-7
ISSN	1875-9777 ; 1934-5909
ISSN (online)	1875-9777
ISSN	1934-5909
DOI	10.1016/j.stem.2022.09.008
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Article: Scalable, accessible, and reproducible reference genome assembly and evaluation in Galaxy.

Larivière, Delphine / Abueg, Linelle / Brajuka, Nadolina / Gallardo-Alba, Cristóbal / Grüning, Bjorn / Ko, Byung June / Ostrovsky, Alex / Palmada-Flores, Marc / Pickett, Brandon D / Rabbani, Keon / Balacco, Jennifer R / Chaisson, Mark / Cheng, Haoyu / Collins, Joanna / Denisova, Alexandra / Fedrigo, Olivier / Gallo, Guido Roberto / Giani, Alice Maria / Gooder, Grenville MacDonald /

Jain, Nivesh / Johnson, Cassidy / Kim, Heebal / Lee, Chul / Marques-Bonet, Tomas / O'Toole, Brian / Rhie, Arang / Secomandi, Simona / Sozzoni, Marcella / Tilley, Tatiana / Uliano-Silva, Marcela / van den Beek, Marius / Waterhouse, Robert M / Phillippy, Adam M / Jarvis, Erich D / Schatz, Michael C / Nekrutenko, Anton / Formenti, Giulio

bioRxiv : the preprint server for biology

2023

Abstract: Improvements in genome sequencing and assembly are enabling high-quality reference genomes for all species. However, the assembly process is still laborious, computationally and technically demanding, lacks standards for reproducibility, and is not ... ...

Abstract	Improvements in genome sequencing and assembly are enabling high-quality reference genomes for all species. However, the assembly process is still laborious, computationally and technically demanding, lacks standards for reproducibility, and is not readily scalable. Here we present the latest Vertebrate Genomes Project assembly pipeline and demonstrate that it delivers high-quality reference genomes at scale across a set of vertebrate species arising over the last ~500 million years. The pipeline is versatile and combines PacBio HiFi long-reads and Hi-C-based haplotype phasing in a new graph-based paradigm. Standardized quality control is performed automatically to troubleshoot assembly issues and assess biological complexities. We make the pipeline freely accessible through Galaxy, accommodating researchers even without local computational resources and enhanced reproducibility by democratizing the training and assembly process. We demonstrate the flexibility and reliability of the pipeline by assembling reference genomes for 51 vertebrate species from major taxonomic groups (fish, amphibians, reptiles, birds, and mammals).
Language	English
Publishing date	2023-06-30
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.06.28.546576
Database	MEDical Literature Analysis and Retrieval System OnLINE

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