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.

The present disclosure includes compositions of a zwitterionic polysaccharide (e.g., B. fragilis capsular polysaccharide A (PSA)) (including active fragments thereof) and methods of treating viral infection and viral infection associated inflammation with compositions of a zwitterionic polysaccharide (e.g., B. fragilis capsular polysaccharide A (PSA)) (including active fragments thereof).

Compositions of and methods of treatment with zwitterionic polysaccharide

Author response: A gut bacterial amyloid promotes α-synuclein aggregation and motor impairment in mice

Background: Epidemiologic studies indicate maternal infection as a risk factor for autism and schizophrenia in the offspring. Maternal immune activation (MIA) in the dam, an animal model for maternal infection, leads the offspring exhibiting autistic- and schizophrenia-like behaviors.
However, the mechanism of how MIA perturbs fetal brain development and precipitates the offspring behavior deficits and brain neuropathologies remains elusive. Prior works demonstrate maternal interleukin-6 (IL-6) is a key cytokine that mediates the effect of MIA on the offspring. Placenta as an interface between dam and fetus presumably plays a role in mediating the acute response to MIA in maternal-placental-fetal axis. Here, we are investigating the role of placental IL-6 activation in the etiology of MIA
caused autistic and schizophrenia-like phenotypes.
Methods: Induction of MIA is done by injecting viral mimic poly(I:C) into the dam at mid-gestation. The inflammatory responses in the fetal brain after poly(I:C) injection is examined to understand the impact of MIA to the brain development. To further investigate the role of placental
IL-6 activation in MIA model, we specifically delete the receptor for IL-6, IL-6Ra, in the placenta of mice. By using placenta-specific IL-6Ra knockout mice, we are allowed to ask whether blocking placental IL-6 activation
can prevent the acute inflammation in the placental-fetal axis and offspring behavioral abnormalities and neuropathologies.
Results: We demonstrate MIA causes acute inflammatory responses in the fetal brain, including increased IL-6 expression and activated IL-6 downstream signaling in fetal prepontine and pontine hindbrain. The acute inflammatory response in the fetal brain following by MIA is found to
depend on IL-6 level in the dam. Knockout of IL-6Ra in the placental trophoblast effectively blocks the inflammation in the placenta and ceases the inflammatory signaling in the fetal brain. Furthermore, the behavioral abnormalities and loss of cerebellar Purkinje cells seen in MIA offspring
were successfully prevented by knockout IL-6Ra in the placental trophoblast.
Conclusion: IL-6 activation in the placenta during maternal infection is indispensible for relaying the inflammatory signal from mother to fetal brain and impacting brain development and adult behaviors. Intervention of IL-6 activation in the placenta after infection could be a potential precaution for offspring developing autism and schizophrenia.

Maternal Immune Activation Perturbs Fetal Brain Development and Adult Behaviors Through Placental Trophoblast IL-6 Activation

Cultivating a Relationship with Gut Bacteria

Increasing evidence suggests a role for the immune system in autism spectrum disorders (ASD) pathogenesis. Studies have reported immune dysregulation in the brain, periphery and gastrointestinal tract in ASD. Furthermore, maternal infection (immune activation, MIA) is a risk factor for ASD. Modelling this risk factor in mice yields offspring with the cardinal behavioral and neuropathological symptoms of human ASD. In this study, we ask if MIA offspring also exhibit abnormal neural, peripheral or enteric immunity. We find that these offspring display altered immune profiles and function. In addition, hematopoietic stem cells (HSCs) from MIA offspring exhibit altered lineage potential and differentiation. To examine whether immune dysfunction contributes to ASD pathogenesis, we behaviorally assess MIA offspring that have been repopulated with naive bone marrow. To explore the potential for prenatal programming of long-term immune dysfunction, we examine whether transferring HSCs from MIA offspring into naive mice can induce cell-autonomous immune abnormalities.

Sarkis K. Mazmanian

Papers

Compositions of and methods of treatment with zwitterionic polysaccharide

Author response: A gut bacterial amyloid promotes α-synuclein aggregation and motor impairment in mice

Maternal Immune Activation Perturbs Fetal Brain Development and Adult Behaviors Through Placental Trophoblast IL-6 Activation

Cultivating a Relationship with Gut Bacteria

119. Modeling an autism risk factor in mice leads to permanent changes in the immune system