scholarly journals Genome-wide prediction of DNA mutation effect on nucleosome positions for yeast synthetic genomics

2020 ◽  
pp. gr.264416.120
Author(s):  
Etienne Routhier ◽  
Edgard Pierre ◽  
Ghazaleh Khodabandelou ◽  
Julien Mozziconacci
Keyword(s):  
Dna Mutation ◽  
Genome Wide ◽  
Synthetic Genomics

scholarly journals Multiple replication origins with diverse control mechanisms in Haloarcula hispanica

2013 ◽  
Vol 42 (4) ◽  
pp. 2282-2294 ◽  
Author(s):  
Zhenfang Wu ◽  
Jingfang Liu ◽  
Haibo Yang ◽  
Hailong Liu ◽  
Hua Xiang
Keyword(s):  
Replication Initiation ◽  
Control Mechanisms ◽  
Replication Origins ◽  
Dna Mutation ◽  
Genome Wide ◽  
Marker Frequency ◽  
Haloarcula Hispanica ◽  
Specific Control ◽  
Main Chromosome ◽  
Multiple Replication

Abstract The use of multiple replication origins in archaea is not well understood. In particular, little is known about their specific control mechanisms. Here, we investigated the active replication origins in the three replicons of a halophilic archaeon, Haloarcula hispanica, by extensive gene deletion, DNA mutation and genome-wide marker frequency analyses. We revealed that individual origins are specifically dependent on their co-located cdc6 genes, and a single active origin/cdc6 pairing is essential and sufficient for each replicon. Notably, we demonstrated that the activities of oriC1 and oriC2, the two origins on the main chromosome, are differently controlled. A G-rich inverted repeat located in the internal region between the two inverted origin recognition boxes (ORBs) plays as an enhancer for oriC1, whereas the replication initiation at oriC2 is negatively regulated by an ORB-rich region located downstream of oriC2-cdc6E, likely via Cdc6E-titrating. The oriC2 placed on a plasmid is incompatible with the wild-type (but not the ΔoriC2) host strain, further indicating that strict control of the oriC2 activity is important for the cell. This is the first report revealing diverse control mechanisms of origins in haloarchaea, which has provided novel insights into the use and coordination of multiple replication origins in the domain of Archaea.

Abstract 3247: Genome-wide cell-free DNA mutation integration for sensitive cancer detection

2018 ◽  
Author(s):  
Asaf Zviran ◽  
Steven T. Hill ◽  
Rafael Schulman ◽  
Minita Shah ◽  
Sunil Deochand ◽  
...  
Keyword(s):  
Cancer Detection ◽  
Cell Free Dna ◽  
Dna Mutation ◽  
Free Dna ◽  
Genome Wide

scholarly journals Genome-wide engineering of an infectious clone of herpes simplex virus type 1 using synthetic genomics assembly methods

2017 ◽  
Vol 114 (42) ◽  
pp. E8885-E8894 ◽  
Author(s):  
Lauren M. Oldfield ◽  
Peter Grzesik ◽  
Alexander A. Voorhies ◽  
Nina Alperovich ◽  
Derek MacMath ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Wild Type Virus ◽  
Genome Wide ◽  
Synthetic Genomics ◽  
Simplex Virus ◽  
Hsv 1

Here, we present a transformational approach to genome engineering of herpes simplex virus type 1 (HSV-1), which has a large DNA genome, using synthetic genomics tools. We believe this method will enable more rapid and complex modifications of HSV-1 and other large DNA viruses than previous technologies, facilitating many useful applications. Yeast transformation-associated recombination was used to clone 11 fragments comprising the HSV-1 strain KOS 152 kb genome. Using overlapping sequences between the adjacent pieces, we assembled the fragments into a complete virus genome in yeast, transferred it into anEscherichia colihost, and reconstituted infectious virus following transfection into mammalian cells. The virus derived from this yeast-assembled genome, KOSYA, replicated with kinetics similar to wild-type virus. We demonstrated the utility of this modular assembly technology by making numerous modifications to a single gene, making changes to two genes at the same time and, finally, generating individual and combinatorial deletions to a set of five conserved genes that encode virion structural proteins. While the ability to perform genome-wide editing through assembly methods in large DNA virus genomes raises dual-use concerns, we believe the incremental risks are outweighed by potential benefits. These include enhanced functional studies, generation of oncolytic virus vectors, development of delivery platforms of genes for vaccines or therapy, as well as more rapid development of countermeasures against potential biothreats.

scholarly journals The co-evolution of the genome and epigenome in colorectal cancer

2021 ◽  
Author(s):  
Andrea Sottoriva ◽  
Timon Heide ◽  
George Cresswell ◽  
Inma Spiteri ◽  
Claire Lynn ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Biology ◽  
Large Scale ◽  
Chromatin Accessibility ◽  
Dna Mutation ◽  
Dna Mutations ◽  
Genome Wide ◽  
Whole Genomes ◽  
Single Clone ◽  
Genetic Tumour

Abstract Colorectal malignancies are a leading cause of cancer death. Despite large-scale genomic efforts, DNA mutations do not fully explain malignant evolution. Here we study the co-evolution of the genome and epigenome of colorectal tumours at single-clone resolution using spatial multi-omic profiling of individual glands. We collected 1,373 samples from 30 primary cancers and 9 concomitant adenomas and generated 1,212 chromatin accessibility profiles, 527 whole-genomes and 297 whole-transcriptomes. We found positive selection for DNA mutations in chromatin modifier genes and recurrent chromatin changes in regulatory regions of cancer drivers with otherwise no mutation. Genome-wide alterations in transcription factor binding accessibility involved CTCF, downregulation of interferon, and increased accessibility for SOX and HOX, indicating developmental genes reactivation. Epigenetic aberrations were heritable, distinguishing adenomas from cancers. Mutational signature analysis showed the epigenome influencing DNA mutation accumulation. This study provides a map of (epi)genetic tumour heterogeneity, with fundamental implications for understanding colorectal cancer biology.

scholarly journals The co-evolution of the genome and epigenome in colorectal cancer

2021 ◽  
Author(s):  
Timon Heide ◽  
Jacob Househam ◽  
Inmaculada Spiteri ◽  
Claire Lynn ◽  
George D Cresswell ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Biology ◽  
Large Scale ◽  
Chromatin Accessibility ◽  
Dna Mutation ◽  
Dna Mutations ◽  
Genome Wide ◽  
Whole Genomes ◽  
Single Clone ◽  
Genetic Tumour

Colorectal malignancies are a leading cause of cancer death. Despite large-scale genomic efforts, DNA mutations do not fully explain malignant evolution. Here we study the co-evolution of the genome and epigenome of colorectal tumours at single-clone resolution using spatial multi-omic profiling of individual glands. We collected 1,373 samples from 30 primary cancers and 9 concomitant adenomas and generated 1,212 chromatin accessibility profiles, 527 whole-genomes and 297 whole-transcriptomes. We found positive selection for DNA mutations in chromatin modifier genes and recurrent chromatin changes in regulatory regions of cancer drivers with otherwise no mutation. Genome-wide alterations in transcription factor binding accessibility involved CTCF, downregulation of interferon, and increased accessibility for SOX and HOX, indicating developmental genes reactivation. Epigenetic aberrations were heritable, distinguishing adenomas from cancers. Mutational signature analysis showed the epigenome influencing DNA mutation accumulation. This study provides a map of (epi)genetic tumour heterogeneity, with fundamental implications for understanding colorectal cancer biology.

Genome-wide screen in yeast to identify modulators of mutant SOD1 toxicity

2008 ◽  
Vol 35 (S 01) ◽  
Author(s):  
D Ubmann ◽  
B Göricke ◽  
L Fichtner ◽  
I Panou ◽  
G.H Braus ◽  
...  
Keyword(s):  
Mutant Sod1 ◽  
Genome Wide
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