Metabolomics Characterization of Human Diseases

Author(s):  
Masahiro Sugimoto
Keyword(s):  
Author(s):  
David Heller ◽  
Martin Vingron ◽  
George Church ◽  
Heng Li ◽  
Shilpa Garg

AbstractSegmental duplications are important for understanding human diseases and evolution. The challenge to distinguish allelic and duplication sequences has hindered their phased assembly as well as characterization of structural variant calls. Here we have developed a novel graph-based approach that leverages single nucleotide differences in overlapping reads to distinguish allelic and duplication sequences information from long read accurate PacBio HiFi sequencing. These differences enable to generate allelic and duplication-specific overlaps in the graph to spell out phased assembly used for structural variant calling. We have applied our method to three public genomes: CHM13, NA12878 and HG002. Our method resolved 86% of duplicated regions fully with contig N50 up to 79 kb and produced <800 structural variant phased calls, outperforming state-of-the-part SDA method in terms of all metrics. Furthermore, we demonstrate the importance of phased assemblies and variant calls to the biologically-relevant duplicated genes such as SMN1, SRGAP2C, NPY4R and FAM72A. Our phased assemblies and accurate variant calling specifically in duplicated regions will enable the study of the evolution and adaptation of various species.


Blood ◽  
2013 ◽  
Vol 121 (16) ◽  
pp. 3246-3253 ◽  
Author(s):  
Jingping Hu ◽  
Jing Liu ◽  
Fumin Xue ◽  
Gregory Halverson ◽  
Marion Reid ◽  
...  

Key Points Purification of staged human erythroblasts should facilitate a comprehensive cellular and molecular characterization of these cell populations. Quantification of human terminal erythropoiesis in vivo provides a powerful means for studying impaired erythropoiesis in human diseases.


2014 ◽  
Vol 151 (1_suppl) ◽  
pp. P69-P69 ◽  
Author(s):  
Leslie Farmer-Shock ◽  
Brandon Gallemore ◽  
Richard Oberto ◽  
Cameron Hinkel ◽  
Tersa Lever
Keyword(s):  

mBio ◽  
2021 ◽  
Author(s):  
Yunjie Chang ◽  
Hui Xu ◽  
Md A. Motaleb ◽  
Jun Liu

Many spirochetes cause serious human diseases. They are well recognized by their distinct morphology and motility.


eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Rati Verma ◽  
Robert S Oania ◽  
Natalie J Kolawa ◽  
Raymond J Deshaies

Ubiquitin-dependent proteolysis can initiate at ribosomes for myriad reasons including misfolding of a nascent chain or stalling of the ribosome during translation of mRNA. Clearance of a stalled complex is required to recycle the ribosome for future use. Here we show that the ubiquitin (Ub) pathway segregase Cdc48/p97 and its adaptors Ufd1-Npl4 participate in ribosome-associated degradation (RAD) by mediating the clearance of ubiquitinated, tRNA-linked nascent peptides from ribosomes. Through characterization of both endogenously-generated and heterologous model substrates for the RAD pathway, we conclude that budding yeast Cdc48 functions downstream of the Ub ligases Ltn1 and Ubr1 to release nascent proteins from the ribosome so that they can be degraded by the proteasome. Defective RAD could contribute to the pathophysiology of human diseases caused by mutations in p97.


2021 ◽  
Author(s):  
Moataz Dowaidar

The recombinant adeno-associated virus (rAAV) has shown tremendous promise in treating major human diseases as a DNA vector. Production capacity, precise and detailed characterization of these complex biologics, and unfavorable immune responses that limit long-term expression are all difficulties that have hindered the development of AAV-based gene therapies. The complex biologics manufacturing process is strongly tied to the quality aspects of the product. Product-related impurities such as empty capsids, AAV-encapsidated residual DNA impurities, and replication-competent AAV are difficult to remove by purification. Empty capsids can contribute to immunotoxicity by increasing the quantity of immune-capsid antibody-AAV complexes that can activate the classical complement system.Parameters of the manufacturing process should be described to determine operating ranges demonstrated to consistently result in the stated requirements of the end product. QC tests must be utilized to verify that each AAV lot generated to assist clinical research fulfills defined requirements. There are certain particular nomenclature concerns for AAV-based products, like residual host cell DNA. Cartersville, Georgia, is a city that is seeking to get back to its fundamentals following a wave of controversy. The city devotes some of its efforts to preserving the community's past.The community is devouring its resources in an attempt to salvage a municipality close to bankruptcy. The city is dedicating around a quarter of a billion dollars to saving the city's economy. It also tries to save its image since the city is set to go bankrupt. The use of RAAV-based gene transfer holds great promise for the treatment of human diseases.


Author(s):  
B. L. Soloff ◽  
T. A. Rado

Mycobacteriophage R1 was originally isolated from a lysogenic culture of M. butyricum. The virus was propagated on a leucine-requiring derivative of M. smegmatis, 607 leu−, isolated by nitrosoguanidine mutagenesis of typestrain ATCC 607. Growth was accomplished in a minimal medium containing glycerol and glucose as carbon source and enriched by the addition of 80 μg/ ml L-leucine. Bacteria in early logarithmic growth phase were infected with virus at a multiplicity of 5, and incubated with aeration for 8 hours. The partially lysed suspension was diluted 1:10 in growth medium and incubated for a further 8 hours. This permitted stationary phase cells to re-enter logarithmic growth and resulted in complete lysis of the culture.


Sign in / Sign up

Export Citation Format

Share Document