A robust correlation estimator and nonlinear recurrent model to infer genetic interactions in Saccharomyces cerevisiae and pathways of pulmonary disease in Homo sapiens

Biosystems ◽  
2009 ◽  
Vol 98 (3) ◽  
pp. 160-175 ◽  
Author(s):  
Cheng-Long Chuang ◽  
Chung-Ming Chen ◽  
Wai-Si Wong ◽  
Kun-Nan Tsai ◽  
Err-Cheng Chan ◽  
...  
2014 ◽  
Vol 42 (15) ◽  
pp. 9838-9853 ◽  
Author(s):  
Saeed Kaboli ◽  
Takuya Yamakawa ◽  
Keisuke Sunada ◽  
Tao Takagaki ◽  
Yu Sasano ◽  
...  

Abstract Despite systematic approaches to mapping networks of genetic interactions in Saccharomyces cerevisiae, exploration of genetic interactions on a genome-wide scale has been limited. The S. cerevisiae haploid genome has 110 regions that are longer than 10 kb but harbor only non-essential genes. Here, we attempted to delete these regions by PCR-mediated chromosomal deletion technology (PCD), which enables chromosomal segments to be deleted by a one-step transformation. Thirty-three of the 110 regions could be deleted, but the remaining 77 regions could not. To determine whether the 77 undeletable regions are essential, we successfully converted 67 of them to mini-chromosomes marked with URA3 using PCR-mediated chromosome splitting technology and conducted a mitotic loss assay of the mini-chromosomes. Fifty-six of the 67 regions were found to be essential for cell growth, and 49 of these carried co-lethal gene pair(s) that were not previously been detected by synthetic genetic array analysis. This result implies that regions harboring only non-essential genes contain unidentified synthetic lethal combinations at an unexpectedly high frequency, revealing a novel landscape of genetic interactions in the S. cerevisiae genome. Furthermore, this study indicates that segmental deletion might be exploited for not only revealing genome function but also breeding stress-tolerant strains.


Genetics ◽  
1997 ◽  
Vol 147 (2) ◽  
pp. 467-478 ◽  
Author(s):  
Gene C Webb ◽  
Marloes Hoedt ◽  
Lynn J Poole ◽  
Elizabeth W Jones

The PEP7 gene from Saccharomyces cerevisiae encodes a 59-kD hydrophilic polypeptide that is required for transport of soluble vacuolar hydrolase precursors from the TGN to the endosome. This study presents the results of a high-copy suppression analysis of pep7-20 mutant phenotypes. This analysis demonstrated that both VPS45 and PEP12 are allele-specific high-copy suppressors of pep7-20 mutant phenotypes. Overexpression of VPS45 was able to completely suppress the Zn2+ sensitivity and partially suppress the carboxypeptidase Y deficiency. Overexpression of PEP12 was able to do the same, but to a lesser extent. Vps45p and Pep12p are Sec1p and syntaxin (t-SNARE) homologues, respectively, and are also thought to function in transport between the TGN and endosome. Two additional vacuole pathway SNARE complex homologues, Vps33p (Sec1p) and Pth1p (syntaxin), when overexpressed, were unable to suppress pep7-20 or any other pep7 allele, further supporting the specificity of the interactions of pep7-20 with PEP12 and VPS45. Because several other vesicle docking/fusion reactions take place in the cell without discernible participation of Pep7p homologues, we suggest that Pep7p is a step-specific regulator of docking and/or fusion of TGN-derived transport vesicles onto the endosome.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Tuc H. M. Nguyen ◽  
Sargunvir Sondhi ◽  
Andrew Ziesel ◽  
Swati Paliwal ◽  
Heather L. Fiumera

Abstract Background Mitochondrial function requires numerous genetic interactions between mitochondrial- and nuclear- encoded genes. While selection for optimal mitonuclear interactions should result in coevolution between both genomes, evidence for mitonuclear coadaptation is challenging to document. Genetic models where mitonuclear interactions can be explored are needed. Results We systematically exchanged mtDNAs between 15 Saccharomyces cerevisiae isolates from a variety of ecological niches to create 225 unique mitochondrial-nuclear genotypes. Analysis of phenotypic profiles confirmed that environmentally-sensitive interactions between mitochondrial and nuclear genotype contributed to growth differences. Exchanges of mtDNAs between strains of the same or different clades were just as likely to demonstrate mitonuclear epistasis although epistatic effect sizes increased with genetic distances. Strains with their original mtDNAs were more fit than strains with synthetic mitonuclear combinations when grown in media that resembled isolation habitats. Conclusions This study shows that natural variation in mitonuclear interactions contributes to fitness landscapes. Multiple examples of coadapted mitochondrial-nuclear genotypes suggest that selection for mitonuclear interactions may play a role in helping yeasts adapt to novel environments and promote coevolution.


2019 ◽  
Vol 30 (9) ◽  
pp. 1069-1084 ◽  
Author(s):  
Danny Mollerup Sørensen ◽  
Henrik Waldal Holen ◽  
Jesper Torbøl Pedersen ◽  
Helle Juel Martens ◽  
Daniele Silvestro ◽  
...  

P5A ATPases are expressed in the endoplasmic reticulum (ER) of all eukaryotic cells, and their disruption results in severe ER stress. However, the function of these ubiquitous membrane proteins, which belong to the P-type ATPase superfamily, is unknown. We purified a functional tagged version of the Saccharomyces cerevisiae P5A ATPase Spf1p and observed that the ATP hydrolytic activity of the protein is stimulated by phosphatidylinositol 4-phosphate (PI4P). Furthermore, SPF1 exhibited negative genetic interactions with SAC1, encoding a PI4P phosphatase, and with OSH1 to OSH6, encoding Osh proteins, which, when energized by a PI4P gradient, drive export of sterols and lipids from the ER. Deletion of SPF1 resulted in increased sensitivity to inhibitors of sterol production, a marked change in the ergosterol/lanosterol ratio, accumulation of sterols in the plasma membrane, and cytosolic accumulation of lipid bodies. We propose that Spf1p maintains cellular sterol homeostasis by influencing the PI4P-induced and Osh-mediated export of sterols from the ER.


Genetics ◽  
2015 ◽  
Vol 199 (4) ◽  
pp. 1023-1033 ◽  
Author(s):  
Stephen K. Godin ◽  
Camille Meslin ◽  
Faiz Kabbinavar ◽  
Dominique S. Bratton-Palmer ◽  
Christina Hornack ◽  
...  

2003 ◽  
Vol 14 (11) ◽  
pp. 4329-4341 ◽  
Author(s):  
April S. Goehring ◽  
David M. Rivers ◽  
George F. Sprague

Ubiquitin is a small modifier protein that is conjugated to substrates to target them for degradation. Recently, a surprising number of ubiquitin-like proteins have been identified that also can be attached to proteins. Herein, we identify two molecular functions for the posttranslational protein modifier from Saccharomyces cerevisiae, Urm1p. Simultaneous loss of Urm1p and Cla4p, a p21-activated kinase that functions in budding, is lethal. This result suggests a role for the urmylation pathway in budding. Furthermore, loss of the urmylation pathway causes defects in invasive growth and confers sensitivity to rapamycin. Our results indicate that the sensitivity to rapamycin is due to a genetic interaction with the TOR pathway, which is important for regulation of cell growth in response to nutrients. We have found that Urm1p can be attached to a number of proteins. Loss of five genes that are also essential in a cla4Δ strain, NCS2, NCS6, ELP2, ELP6, and URE2, affect the level of at least one Urm1p conjugate. Moreover, these five genes have a role in invasive growth and display genetic interactions with the TOR pathway. In summary, our results suggest the urmylation pathway is involved in nutrient sensing and budding.


2020 ◽  
Author(s):  
Tuc H.M. Nguyen ◽  
Sargunvir Sondhi ◽  
Andrew Ziesel ◽  
Swati Paliwal ◽  
Heather Fiumera

Abstract Background: Mitochondrial function requires numerous genetic interactions between mitochondrial- and nuclear- encoded genes. While selection for optimal mitonuclear interactions should result in coevolution between both genomes, evidence for mitonuclear coadaptation is challenging to document. Genetic models where mitonuclear interactions can be explored are needed. Results: We systematically exchanged mtDNAs between 15 Saccharomyces cerevisiae isolates from a variety of ecological niches to create 225 unique mitochondrial-nuclear genotypes. Analysis of phenotypic profiles confirmed that environmentally-sensitive interactions between mitochondrial and nuclear genotype contributed to growth differences. Exchanges of mtDNAs between strains of the same or different clades were just as likely to demonstrate mitonuclear epistasis although epistatic effect sizes increased with genetic distances. Strains with their original mtDNAs were more fit than strains with synthetic mitonuclear combinations when grown in media that resembled isolation habitats. Conclusions: This study shows that natural variation in mitonuclear interactions contributes to fitness landscapes. Multiple examples of coadapted mitochondrial-nuclear genotypes suggest that selection for mitonuclear interactions may play a role in helping yeasts adapt to novel environments and promote coevolution.


F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1200
Author(s):  
Mark Wong ◽  
Rhodri Leng

This paper describes a unique two-step methodology used to construct six linked bibliometric datasets covering the sequencing of Saccharomyces cerevisiae, Homo sapiens, and Sus scrofa genomes. First, we retrieved all sequence submission data from the European Nucleotide Archive (ENA), including accession numbers associated with each species. Second, we used these accession numbers to construct queries to retrieve peer-reviewed scientific publications that first linked to these sequence lengths in the scientific literature. For each species, this resulted in two associated datasets: 1) A .csv file documenting the PMID of each article describing new sequences, all paper authors, all institutional affiliations of each author, countries of institution, year of first submission to the ENA, and the year of article publication, and 2) A .csv file documenting all institutions submitting to the ENA, number of nucleotides sequenced, number of submissions per institution in a given year, and years of submission to the database. In several upcoming publications, we utilise these datasets to understand how institutional collaboration shaped sequencing efforts, and to systematically identify important institutions and changes in network structures over time. This paper, therefore, should aid researchers who would like to use these data for future analyses by making the methodology that underpins it transparent. Further, by detailing our methodology, researchers may be able to utilise our approach to construct similar datasets in the future.


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