scholarly journals Final Report: A Flexible Sequency Reconstructor for Large-Scale DNA Sequencing Projects, September 1, 1994 - August 31, 1999

1999 ◽  
Author(s):  
Susan Miller ◽  
Gene Myers
Keyword(s):  
Dna Sequencing ◽  
Large Scale ◽  
Final Report

scholarly journals Investigating structure function relationships in the NOTCH family through large-scale somatic DNA sequencing studies

2020 ◽  
Author(s):  
Michael W J Hall ◽  
David Shorthouse ◽  
Philip H Jones ◽  
Benjamin A Hall
Keyword(s):  
Dna Sequencing ◽  
Structure Function ◽  
Calcium Binding ◽  
Large Scale ◽  
Driver Mutations ◽  
Missense Mutations ◽  
Mutant Selection ◽  
Ligand Interaction ◽  
Binding Interface

AbstractThe recent development of highly sensitive DNA sequencing techniques has detected large numbers of missense mutations of genes, including NOTCH1 and 2, in ageing normal tissues. Driver mutations persist and propagate in the tissue through a selective advantage over both wild-type cells and alternative mutations. This process of selection can be considered as a large scale, in vivo screen for mutations that increase clone fitness. It follows that the specific missense mutations that are observed in individual genes may offer us insights into the structure-function relationships. Here we show that the positively selected missense mutations in NOTCH1 and NOTCH2 in human oesophageal epithelium cause inactivation predominantly through protein misfolding. Once these mutations are excluded, we further find statistically significant evidence for selection at the ligand binding interface and calcium binding sites. In this, we observe stronger evidence of selection at the ligand interface on EGF12 over EGF11, suggesting that in this tissue EGF12 may play a more important role in ligand interaction. Finally, we show how a mutation hotspot in the NOTCH1 transmembrane helix arises through the intersection of both a high mutation rate and residue conservation. Together these insights offer a route to understanding the mechanism of protein function through in vivo mutant selection.

scholarly journals LDRD final report : robust analysis of large-scale combinatorial applications.

2007 ◽  
Author(s):  
Robert D. Carr ◽  
Todd Morrison ◽  
William Eugene Hart ◽  
Nicolas L. Benavides ◽  
Harvey J. Greenberg ◽  
...  
Keyword(s):  
Large Scale ◽  
Final Report ◽  
Robust Analysis
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