抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

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

Motivation: In 2001 and 2002, we published two papers (Bioinformatics, 17, 282--283, Bioinformatics, 18, 77--82) describing an ultrafast protein sequence clustering program called cd-hit. This program can efficiently cluster a huge protein database with millions of sequences. However, the applications of the underlying algorithm are not limited to only protein sequences clustering, here we present several new programs using the same algorithm including cd-hit-2d, cd-hit-est and cd-hit-est-2d. Cd-hit-2d compares two protein datasets and reports similar matches between them; cd-hit-est clusters a DNA/RNA sequence database and cd-hit-est-2d compares two nucleotide datasets. All these programs can handle huge datasets with millions of sequences and can be hundreds of times faster than methods based on the popular sequence comparison and database search tools, such as BLAST.

Availability: http://cd-hit.org

Contact: [email protected]

Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences

Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.

/pdf/enterotypes-of-the-human-gut-microbiome-55a88sj7we.pdf

Enterotypes of the human gut microbiome

We have analyzed 5,088 bacterial 16S rRNA gene sequences from the distal intestinal (cecal) microbiota of genetically obese ob/ob mice, lean ob/+ and wild-type siblings, and their ob/+ mothers, all fed the same polysaccharide-rich diet. Although the majority of mouse gut species are unique, the mouse and human microbiota(s) are similar at the division (superkingdom) level, with Firmicutes and Bacteroidetes dominating. Microbial-community composition is inherited from mothers. However, compared with lean mice and regardless of kinship, ob/ob animals have a 50% reduction in the abundance of Bacteroidetes and a proportional increase in Firmicutes. These changes, which are division-wide, indicate that, in this model, obesity affects the diversity of the gut microbiota and suggest that intentional manipulation of community structure may be useful for regulating energy balance in obese individuals.

/pdf/obesity-alters-gut-microbial-ecology-31owgafp2h.pdf

Obesity alters gut microbial ecology

The use of selection in recovery of transgenic targets for mutation analysis

Disclosed is a process of screening clones having DNA from an uncultivated microorganism for a specified protein, e.g. enzyme, activity by screening for a specified protein, e.g. enzyme, activity in a library of clones prepared by (i) recovering DNA from a DNA population derived from at least one uncultivated microorganism; and (ii) transforming a host with recovered DNA to produce a library of clones which is screened for the specified protein, e.g. enzyme, activity.

Gene expression library produced from DNA from uncultivated microorganisms and methods for making the same

Differential expression of the genes for the mitochondrial and cytosolic forms of phosphoenolpyruvate carboxykinase.

Spontaneous mutant frequency in livers of two transgenic mouse strains, each carrying identical lambda shuttle vectors with a lacI target gene, was evaluated by two laboratories. These studies investigated variability in spontaneous mutant frequency between animals and as a function of the number of phage screened. Liver DNA was independently isolated from 7–11 week old C 57 BL 6 and B6C3F1 Big Blue® transgenic mice. At least 500 000 phage were screened for mutation at lacI for each animal using standardized assay procedures. In the two labs, the C 57 BL 6 liver spontaneous mutant frequency was 45 ± 9 × 10−6 and 41 ± 7 × 10−6. The B6C3F1 liver spontaneous mutant frequency was 42 ± 10 × 10−6 at one lab and 43 ± 12 × 10−6 and 41 ± 8 × 10−6 in two trials at the second lab. Mean mutant frequency data from both labs, calculated in increments of 100 000 plaque forming units (pfu) scored for each mouse strain, show stabilized mean mutant frequency and standard deviation after approximately 200 000–300 000 pfu screened. The frequency of spontaneous lacI mutants was reproducible both within and between labs and was comparable between the two transgenic mouse strains.

Interlaboratory comparison: liver spontaneous mutant frequency from lambda/lacI transgenic mice (Big Blue®) (II)

A transgenic animal is constructed in which one or more cells contain a promoter to the gene for cytosolic PEPCK operably linked to a non-PEPCK gene of interest. Expression of this gene is controlled by modifying the protein and carbohydrate components of the animal's diet, or by direct hormonal regulation. The PEPCK promoter is induced by high protein and inhibited by high carbohydrate, or more directly by cAMP and insulin. The linked gene is expressed essentially only after birth and essentially only in particular tissues. The PEPCK promoter has an extremely high promoter strength.

Dietary and hormonal regulation of expression of exogenous genes in transgenic animals under control of the promoter of the gene for phosphoenolpyruvate carboxykinase

Jay M. Short

Papers

The use of selection in recovery of transgenic targets for mutation analysis

Gene expression library produced from DNA from uncultivated microorganisms and methods for making the same

Differential expression of the genes for the mitochondrial and cytosolic forms of phosphoenolpyruvate carboxykinase.

Interlaboratory comparison: liver spontaneous mutant frequency from lambda/lacI transgenic mice (Big Blue®) (II)

Dietary and hormonal regulation of expression of exogenous genes in transgenic animals under control of the promoter of the gene for phosphoenolpyruvate carboxykinase