Bacterial viruses, more than just a proxy for the microbiome

Attempts to study the viruses of the human microbiome (virome) have followed a similar path to the study of the microbiome itself – although with a time lag due to the additional complexities of studying viruses. First, there was an exploration of what is present in humans, followed by efforts to correlate shifts in the virome to aspects of health. The field is only just beginning to work towards establishing causal links between viruses and observable phenotypes in humans.

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Summary Figure, Norman et al 2015, Cell

The 2015 Norman et al. paper in Cell was a landmark study for the field of virome research, representing one of the first rigorous approaches to virome characterization in health and disease. Through sequencing of fecal filtrates, they were able to correlate the abundance and diversity of bacterial viruses to those of the fecal bacterial community. Because bacterial viruses can only exist in the presence of their hosts, it was surprising to find that as the bacterial community became less diverse in disease, the viral community did the opposite! This discrepancy justifies the study of the viral community not simply as a proxy for the bacterial community, but also for its own potential diagnostic and therapeutic merits.

Please join us on Friday May 24th, 2018 at 3:00PM in HSC 3N10A to examine the findings of this paper and discuss:

  1. Sequencing the virome, and extracting meaningful data from it
  2. Hypotheses as to drivers of changes in bacterial virus diversity
  3. Implications of these findings on future virome research, especially in health .

Paper Citation:

Norman, J.M., Handley, S.A., Baldridge, M.T., Droit, L., Liu, C.Y., Keller, B.C., et al. (2015) Disease-specific alterations in the enteric virome in inflammatory bowel disease. Cell 160: 447–460 http://dx.doi.org/10.1016/j.cell.2015.01.002.

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Using Strain-Level Analyses to Understand Maternal Seeding of the Microbiome

The infant gut is rapidly colonized by microbes shortly after birth and the community that is established in early life may shape later gut microbial populations. The vertical transmission of bacteria from mother to infant at birth plays an important role in early infant development. However, in order to understand the transmission of bacterial strains from mother to infant, tracking of strictly defined unique microbial strains is required. Further insight into the vertical transmission of strains will allow us to clarify how intestinal bacteria emerge, how long they persist after colonization, and the impact of colonization by other strains from the environment.

In their recent paper, Korpela et al. use rare marker single nucleotide variants to track maternal transmission of strains and their persistence during infant development. They assessed strain persistence and intra-family strain transmissions at birth and later in life. Using rare single nucleotide variants in fecal metagenomes of infants and their family members, they show evidence of selective and persistent transmission of maternal strain populations as well as occasional replacement by strains from the environment in later childhood.

Please join us on Friday April 27, 2018 at 3:00PM in HSC 3N10A to examine the findings of this paper and discuss:

  1. Use of rare marker SNVs to track transmission of strains
  2. The effect of C-sections on maternal seeding
  3. Strain transmission in adulthood

Paper Citation: Korpela, K., Costea, P., Coelho, L. P., Kandels-Lewis, S., Willemsen, G., Boomsma, D. I., … & Bork, P. (2018). Selective maternal seeding and environment shape the human gut microbiome. Genome research28(4), 561-568.

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Are we studying the ecology of molecules rather than of microbes?

This week’s journal club paper was the focus of an mBio editorial entitled “In Nature, There Is Only Diversity” that discusses the abstraction of biological concepts such as microbial species and strain by marker gene sequencing and the operational taxonomic unit (OTU). In their article Chase et al. (2017) assess one abundant bacterial OTU within forest communities which that splits into six distinct clades based on gene and protein features from complete genomes. The authors then map the biogeography of these clades across environmental gradients with the use of metagenomics. This paper highlights that when we use marker genes as a proxy for phylogenetic relatedness, the traits that we care about must also track with differences in the marker genes used, which is often not the case. These concepts will be discussed at 3pm on Friday March 23rd in HSC 3N10A. Specifically:

  1. How each phenotype mapped with phylogeny
  2. How phylogeny was measured and compared to OTU diversity
  3. What OTU diversity can and cannot tell us in this example
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Human Microbiome working group 2018

The Microbiome Working Group has moved back to Tuesdays! This is a weekly, drop-in, work/discussion hour that aims to bring microbiome researchers together –  independent of sample type, laboratory, or skill level. This isn’t a meeting and there are no presentations. This is about getting research and analysis done. Bring your laptop and use the presence of like-minded others as motivation.

Everyone is welcome, no need to sign up!

Winter 2018: Tuesdays 3:30-4:30 pm HSC 1J9A

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2in1: Assembly benchmarking and evaluation

The numbers of metagenomics studies are exponentially increasing in recent years. Because we lack comprehensive microbial genome databases for most environments, the microbiome field is moving towards de novo metagenomics, using reference-independent techniques to assemble putative genes and in silico refinement of draft genomes from short shotgun sequencing reads. The challenges with this technique are to critically assess the quality of assembly and to avoid chimeric contigs, which can result from sequencing or assembly errors.

On Friday, November 24 at 3pm in 3N10A, at the human microbiome journal club, we will review the performance of popular assembly algorithms using two benchmarking studies: Van der Walt et. al. (2017) that evaluated the metagenomics assembly using defined microbial communities and Greenwald et. al. (2017) which proposed a workflow to select metagenomic assembler based on the research question, the computational resources available and the bioinformatic expertise of the researcher.

More specifically, we will discuss
1. What are the criteria to critically assess the quality of a metagenomic assembly?
2. Why is it necessary to compare the performance of multiple algorithms for a given dataset?
3. What is the required computational power to conduct de novo assembly?

Hopefully, by the end of this week’s journal club, we’ll excite you enough that you will join us to continue our discussion over a beer at the Bioinformatics and Beers meet up at The Phoenix.

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Can the development of the gut microbiome of infants impact their future health?

Researchers from the University of Alberta have investigated factors which contribute to the deviation of a normal infant gut microbiome and how these deviated gut microbiomes may have the ability to predict future health including food allergies. Significance analysis of microarrays (SAM) was used to quantify the gut microbial abundance of infants over time, specifically exploring factors of birth mode (cesarean section or vaginal delivery), feeding status (breastfed or formula-fed), and antibiotic exposure.

Please join on Friday October 27, 2017 from 3:00 to 4:00PM in HSC 3N10A as we will discuss:
1. What is perceived as a normal infant gut microbiome?
2. What is SAM and what are the strengths and weaknesses of using SAM in analysis?
3. Could other mechanism be used to study microbial community development over time?

https://www.frontiersin.org/articles/10.3389/fped.2017.00200/full

Yasmin, F. et. al. (2017). Cesarean Section, Formula Feeding, and Infant Antibiotic Exposure: Separate and Combined Impacts on Gut Microbial Changes in Later Infancy. Frontiers in Pediatrics, 5, 200. http://doi.org/10.3389/fped.2017.00200

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Reminder: HMJC This Week!

Just a little reminder that the Human Microbiome Journal Club is meeting, unusually, this week!

We’ll be discussing Gloor & Reid and compositional data analysis in HSC 3N10A at 3 p.m. on Friday, September 15. Check out the original post here.

Because of the unusual week, the monthly Bioinformatics and Beers meetup at the Phoenix is immediately afterwards at 4. Come join us for both!

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September journal club moved to Friday, September 15

Please note that the September Human Microbiome Journal Club has been rescheduled to Friday, September 15 at 3 p.m.

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September 15: Gloor & Reid’s Compositional Data Analysis

This month’s Human Microbiome Journal Club has been cancelled due to an outbreak of vacationitis, but we will resume next month on Friday, September 15 at 3 p.m. in HSC 3N10A.

At the end of September, we’ll be discussing Gloor and Reid’s 2016 paper, Compositional analysis: a valid approach to analyze microbiome high-throughput sequencing data. Gloor and Reid claim that all next-generation sequencing (NGS) data sets are compositional, and that existing ad-hoc statistical tools invented to analyze RNASeq, ChIP-Seq, microbiome, and other NGS data sets should be replaced with more standard tools that account for the data sets’ compositional nature.

Failing to account for the compositionality of a dataset can lead to spurious apparent differential abundances, badly mismeasured correlations among features, and mis-clustering of samples. Gloor and Reid discuss these effects, and propose as a solution the centre-log ratio transformation. ALDEx2 and ANCOM are two R packages discussed in the paper that implement this transformation, and we’ll discuss what they do similarly, what they do differently, and how they compare to DESeq2.

I’ll take us through the paper, and we’ll discuss

  1. The effects of compositionality apparent structure
  2. The function and motivation of log-ratio transformations and
  3. The assumptions this normalization technique implicitly makes about the data, and whether it actually helps us answer the biological questions we’re interested in.

Come join the discussion Friday, September 15 at 3 p.m. in HSC 3N10A.

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Working Group is Moving!

The microbiome working group is a drop in space to support anyone working with microbiome data who feels that they could use some advice or instruction. The intent is for people to help each other and everyone who uses the group is encouraged to attend weekly so that they can pass on what they’ve learned to the new attendees. In the past we’ve gathered on Tuesdays but starting next week working group will move to Mondays from 3:30 – 4:30 pm in HSC 4N52A.  I hope to see you all there!

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