The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.

/pdf/metagenomic-biomarker-discovery-and-explanation-x530ilzkca.pdf

Metagenomic biomarker discovery and explanation

The Human Microbiome Project Consortium reports the first results of their analysis of microbial communities from distinct, clinically relevant body habitats in a human cohort; the insights into the microbial communities of a healthy population lay foundations for future exploration of the epidemiology, ecology and translational applications of the human microbiome.

/pdf/structure-function-and-diversity-of-the-healthy-human-4mecpxyl8r.pdf

Structure, function and diversity of the healthy human microbiome

Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.

A strategy to understand the microbial components of the human genetic and metabolic landscape and how they contribute to normal physiology and predisposition to disease.

/pdf/the-human-microbiome-project-1armeyuv2c.pdf

The human microbiome project.

Intestinal intraepithelial lymphocytes (IELs) form an unconventional T cell population demarcated by agonistic selection in the thymus before populating the gut mucosa, where it is thought they contribute in surveillance, homeostasis, and epithelial repair. Although IELs have been implicated in diseases affecting the gut, much remains to be understood about their selection and specificity. Integrating T cell receptor (TCR) repertoire sequencing and transcriptional profiling, we identify characteristic TCR features of induced CD4-, CD8-, and natural-IEL subsets and furthermore describe for the first time the human natural IEL subset. Depletion of microbial and dietary antigens alone or in combination did little to affect the underlying structure of each subset’s TCR repertoire. In contrast, disruption of β2m-dependent pathways abrogated public features that distinguished the natural IEL repertoires. These findings support a model for imprinting of TCRαβ-IEL repertoires based on competition among similar clonotypes selected for specificity to ubiquitous, conserved, β2m-dependent self-antigens.

Intestinal Intraepithelial Lymphocyte Repertoires are Imprinted Clonal Structures Selected for MHC Reactivity

http://www.cell.com/article/S096098222201750X/pdf

Gut microbiota suppress feeding induced by palatable foods

Effect of oral versus injectable disease-modifying therapies on the epigenome-wide DNA methylation and gut microbiota in multiple sclerosis patients

Changes in gut microbial composition have been linked to inflammatory bowel disease, obesity and allergies in humans. A new study shows that pattern recognition of commensal bacteria by B cells reduces allergic inflammation in mice, adding to the mounting evidence for the 'hygiene hypothesis' (pages 538–546).

/pdf/breathe-easy-microbes-protect-from-allergies-20ju2481q8.pdf

Breathe easy: microbes protect from allergies

Disclosed herein are methods and compositions that can be used to improve motor deficits and neuroinflammation in subjects in need, for example subjects suffering from neurodegenerative disorders (e.g., Parkinson's disease). Also disclosed are methods and compositions that can be used to diagnose neurodegenerative disorders, such as Parkinson's disease.

Sarkis K. Mazmanian

Papers

Intestinal Intraepithelial Lymphocyte Repertoires are Imprinted Clonal Structures Selected for MHC Reactivity

Gut microbiota suppress feeding induced by palatable foods

Effect of oral versus injectable disease-modifying therapies on the epigenome-wide DNA methylation and gut microbiota in multiple sclerosis patients

Breathe easy: microbes protect from allergies

Regulate gut microbiota to treat neurodegenerative disorders