Chronic Wound Mycobiome

A new paper has just come out in mBio, and it represents an exploration of the fungi associated with chronic foot wounds in diabetic patients. This paper represents the last project for which I did benchwork before becoming all 'computational' all the time! I designed the approach for using MiSeq to sequence fungal ITS1 (which included designing and testing new primers specific for the platform) and executed the benchwork along with the first round of computational analyses. I appreciate Michael Loesche and Lindsay Kalan picking it up and performing a lot of necessary work to properly finish it off after I moved on from my position in the Grice Lab at the University of Pennsylvania.

The major finding was that certain aspects of the 'mycobiome' (i.e., the full set of fungi present) are associated with delayed healing, indicating that fungal profiling could become an important aspect of chronic wound care as medicine moves forward. Have a look at the link at the bottom of this post!

Pathogens are associated with poor outcomes. Mean proportion of pathogens (y axis) by end of study reason (x axis). Error bars indicate standard errors of the means.

- Brendan

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Reference:

Kalan, L., M. A. Loesche, B. P. Hodkinson, K. P. Heilmann, G. Ruthel, S. E. Gardner, and E. A. Grice. 2016. Redefining the chronic wound microbiome: fungal communities are prevalent, dynamic, and associated with delayed healing. mBio 7(5): e01058-16.
Download publication (PDF file)

Cancer and HIV

We are at a point in time when the field of cancer research is becoming dominated by immunoncology - the study of how cancer interacts with the immune system.  One interesting aspect of this is that certain viral infections and certain cancer types might be most effectively treated using some of the same cellular and molecular machinery.  This CNN article addresses this in the context of HIV + acute myeloid leukemia and specifically mentions the generation and maintenance of CD8 T-cells as one way of combating both viral infections and specific types of cancer:
http://www.cnn.com/2016/07/15/health/cancer-research-hiv-cure/

- Brendan

Why Design Matters

Recently an article resulting from some of my research at the University of Pennsylvania was published.  It highlights how methods, approach, and experimental design can heavily influence the conclusions of studies on microbial communities.  Specifically, it shows that the most common primers used for microbiome studies (amplifying the 16S-V4 region) do a poor job of amplifying DNA from certain crucial microbes in the skin microbiome (such as Propionibacterium), biasing results and giving an overall inaccurate picture of skin microbial diversity.  A related observation was that the species of Staphylococcus could not be reliably identified using the V4 region, as shown here:

Relative abundance of Staphylococcus sequences able to be classified at the species level. (Top) Staphylococcus species in the Whole Metagenomic Sequence dataset were classified using MetaPhlAn. (Middle and Bottom) 16S-V1-V3 and 16S-V4 species level classifications were determined by pplacer. Pie charts depict the percentage of sequences classified as Staphylococcus at the genus level that were further classified at the species level.

To read a lengthier summary of the article, check out my friend and co-author Geof Hannigan's blog post!

- Brendan

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Reference

Meisel, J., G. D. Hannigan, A. Tyldsley, A. J. SanMiguel, B. P. Hodkinson, Q. Zheng, and E. A. Grice. 2016. Skin microbiome surveys are strongly influenced by experimental design. Journal of Investigative Dermatology DOI: 10.1016/j.jid.2016.01.016.
Download manuscript (PDF file)