Much of what we know about the human microbiome – the microbial communities associated with various parts of our bodies – comes from genome sequencing. Here, DNA is extracted from all cells in samples collected from various body sites and randomly sequenced, typically generating huge volumes of short-read sequencing data. These reads thus represent a random, mixed snapshot of genes encoded within any cell in the original sample. As human cells are commonly collected along with the bacteria, researchers first remove human DNA sequences from the dataset. To do this, they computationally remove any reads that are highly similar to the human reference genome; the remaining gene sequences are then assumed to belong to the microbial community. Researchers studying the human microbiome have frequently been interested to find that these bacterial communities seem to contain a number of highly unusual genes that are unique to human-associated microbes. a) Briefly describe one feature of the short sequences that you might look for to classify it as being “unusual” for a bacterium or not. b) You are tasked with re-analyzing an existing human microbiome sequencing dataset, using the recently released complete human Y chromosome reference sequence instead of the previous assembly. Do you expect your re-analysis to show more, less, or the same amount of “unusual” bacterial sequences? Briefly justify your answer.
Much of what we know about the human microbiome – the microbial communities associated with various parts of our bodies – comes from genome sequencing. Here, DNA is extracted from all cells in samples collected from various body sites and randomly sequenced, typically generating huge volumes of short-read sequencing data. These reads thus represent a random, mixed snapshot of genes encoded within any cell in the original sample.
As human cells are commonly collected along with the bacteria, researchers first remove human DNA sequences from the dataset. To do this, they computationally remove any reads that are highly similar to the human reference genome; the remaining gene sequences are then assumed to belong to the microbial community. Researchers studying the human microbiome have frequently been interested to find that these bacterial communities seem to contain a number of highly unusual genes that are unique to human-associated microbes.
a) Briefly describe one feature of the short sequences that you might look for to classify it as being “unusual” for a bacterium or not.
b) You are tasked with re-analyzing an existing human microbiome sequencing dataset, using the recently released complete human Y chromosome reference sequence instead of the previous assembly. Do you expect your re-analysis to show more, less, or the same amount of “unusual” bacterial sequences? Briefly justify your answer.
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