A term we heard a bunch at the Emory Microbiome Symposium in November was â€œmetagenomicsâ€. Time for an explainer, with some help from Emory geneticist Tim Read.
Nature Reviews Microbiology defines metagenomics as â€œgenomic analysis of microbial DNA that is extracted directly from communities in environmental samples.â€
This technology â€” genomics on a huge scale â€” enables a survey of the different microorganisms present in a specific environment, such as water or soil, to be carried out. Metagenomics is also emerging as a tool for clinical diagnosis of infectious diseases.
Read notes that the term specifically refers to â€œshotgunâ€ sequencing of environmental DNA.
â€œThe shotgun approach is to randomly sample small pieces of the DNA in the tube, no matter which organism they came from,â€ he says. â€œThe output is a mÃ©lange of different genes from bacteria, viruses, fungi, plants and humans.Â The data is fascinating but the analysis is daunting.â€ Read more
As a followup to yesterday’s post on following troublemaker cells in patients with lupus, we’d like to highlight a recent paper in Blood that takesÂ a similar approach to studying how the immune system comes back after bone marrow/blood stem cell transplant.
Leslie Kean, MD, PhD
The paper’sÂ findings have implications for making this type ofÂ transplant safer and preventing graft-versus-host disease.Â In a bone marrow/blood stem cell transplant, to fight cancer, doctors are essentially clearing out someone’s immune system and then “planting” a newÂ oneÂ with the help of a donor. What this paper shows is how much CMV (cytomegalovirus) distorts the new immune system.
CMV is often thought of asÂ harmless — most adults in the United States have been infected with CMV by age 40 and don’t get sick because of it. But in this situation, CMV’s emergence from the shadows forces some of the new TÂ cells to multiply, dominating the immune system so much that it creates gaps in the rest of the T cell repertoire, which canÂ compromise protective immunity. Other seemingly innocuous viruses like BK cause trouble in immunosuppressed patients afterÂ kidney transplant.
The senior author, Leslie Kean, moved from Emory to Seattle Children’s Hospital in 2013, and her team began these studies here in 2010Â (a host of Emory/Winship hematologists and immunologists are co-authors).Â This paperÂ is sort of a mirror image of the Nature Immunology paper on lupus because it also uses next-generation sequencing to follow immune cells with DNA rearrangements — in this case, T cells. Read more
The increasing clinical use of next generation sequencing, especially whole exome and whole genome, continues to be a hot topic. The ability to contribute to diagnosis, clinical utility, incidental findings and whether insurance will cover next-gen sequencing are all changing.
A Nature Medicine article lays out a lot of the emerging business issues on next-gen sequencing. On the topic of incidental findings, Buzzfeed science editor Virginia Hughes last week reported stories of women who receive a cancer diagnosis as a result of having a prenatal genetic test.
â€œThese cases, though extremely rare, are raising ethical questions about the unregulated â€“ and rapidly evolving â€“ genetic-testing industry,â€ Buzzfeed says.
At a recent Department of Pediatrics seminar, Emory geneticist Michael Gambello described examples of how whole exome sequencing, performed to diagnose intellectual disability or developmental problems in a child, can uncover cancer or neurodegenerative disease risk mutations in a parent. The question becomes, whether to notify the parent for something that may or may not be actionable. This is why Emory Genetics Laboratoryâ€™s whole exome sequencing service has an extensive â€œopt-in/opt-outâ€ consent process.
Emory Genetics Laboratory executive director Madhuri Hegde, working with the Association of Molecular Pathology, has been a leader in pushing genetic testing laboratories to adopt best practices. Read more
Emory biochemist Eric Ortlund participated in a study that was recently published in Proceedings of the National Academy of Sciences, which involves tinkering with billions of years of evolution by introducing mutations into DNA polymerase.
What may soon be old-fashioned: next-generation sequencing combines many reactions like the one depicted above into one pot
DNA polymerases, enzymes that replicate and repair DNA, assemble individual letters in the genetic code on a template. The PNAS paper describes efforts to modify Taq DNA polymerase to get it to accept “reversible terminators.” (Taq = Thermus aquaticus, a variety of bacteria that lives in hot springs and thus has heat-resistant enzymes, a useful property for DNA sequencing)
Ortlund was involved because he specializes in looking at how evolution shapes protein structure. Along with co-author Eric Gaucher, Ortlund is part of the Fundamental and Applied Molecular Evolution Center at Emory and the Georgia Institute of Technology.
To sequence DNA faster and more cheaply, scientists are trying to get DNA polymerases to accept new building blocks. This could facilitate next-generation sequencing technology that uses “reversible terminators” to sequence many DNA templates in parallel.
Posted on January 20, 2010
by Quinn Eastman