The Carbohydrate-Active Enzymes database (CAZy; http://www.cazy.org) provides online and continuously updated access to a sequence-based family classification linking the sequence to the specificity and 3D structure of the enzymes that assemble, modify and breakdown oligo- and polysaccharides. Functional and 3D structural information is added and curated on a regular basis based on the available literature. In addition to the use of the database by enzymologists seeking curated information on CAZymes, the dissemination of a stable nomenclature for these enzymes is probably a major contribution of CAZy. The past few years have seen the expansion of the CAZy classification scheme to new families, the development of subfamilies in several families and the power of CAZy for the analysis of genomes and metagenomes. This article outlines the changes that have occurred in CAZy during the past 5 years and presents our novel effort to display the resolution and the carbohydrate ligands in crystallographic complexes of CAZymes.

/pdf/the-carbohydrate-active-enzymes-database-cazy-in-2013-37p3bw39e7.pdf

The carbohydrate-active enzymes database (CAZy) in 2013

Complex carbohydrates of plants are the main food sources of animals and microbes, and serve as promising renewable feedstock for biofuel and biomaterial production. Carbohydrate active enzymes (CAZymes) are the most important enzymes for complex carbohydrate metabolism. With an increasing number of plant and plant-associated microbial genomes and metagenomes being sequenced, there is an urgent need of automatic tools for genomic data mining of CAZymes. We developed the dbCAN web server in 2012 to provide a public service for automated CAZyme annotation for newly sequenced genomes. Here, dbCAN2 (http://cys.bios.niu.edu/dbCAN2) is presented as an updated meta server, which integrates three state-of-the-art tools for CAZome (all CAZymes of a genome) annotation: (i) HMMER search against the dbCAN HMM (hidden Markov model) database; (ii) DIAMOND search against the CAZy pre-annotated CAZyme sequence database and (iii) Hotpep search against the conserved CAZyme short peptide database. Combining the three outputs and removing CAZymes found by only one tool can significantly improve the CAZome annotation accuracy. In addition, dbCAN2 now also accepts nucleotide sequence submission, and offers the service to predict physically linked CAZyme gene clusters (CGCs), which will be a very useful online tool for identifying putative polysaccharide utilization loci (PULs) in microbial genomes or metagenomes.

/pdf/dbcan2-a-meta-server-for-automated-carbohydrate-active-3r2okely9h.pdf

dbCAN2: a meta server for automated carbohydrate-active enzyme annotation

The gut microbiota benefits humans via short-chain fatty acid (SCFA) production from carbohydrate fermentation, and deficiency in SCFA production is associated with type 2 diabetes mellitus (T2DM). We conducted a randomized clinical study of specifically designed isoenergetic diets, together with fecal shotgun metagenomics, to show that a select group of SCFA-producing strains was promoted by dietary fibers and that most other potential producers were either diminished or unchanged in patients with T2DM. When the fiber-promoted SCFA producers were present in greater diversity and abundance, participants had better improvement in hemoglobin A1c levels, partly via increased glucagon-like peptide-1 production. Promotion of these positive responders diminished producers of metabolically detrimental compounds such as indole and hydrogen sulfide. Targeted restoration of these SCFA producers may present a novel ecological approach for managing T2DM.

http://science.sciencemag.org/content/sci/359/6380/1151.full.pdf

Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes

The gut is home to trillions of microorganisms that have fundamental roles in many aspects of human biology, including immune function and metabolism. The reduced diversity of the gut microbiota in Western populations compared to that in populations living traditional lifestyles presents the question of which factors have driven microbiota change during modernization. Microbiota-accessible carbohydrates (MACs) found in dietary fibre have a crucial involvement in shaping this microbial ecosystem, and are notably reduced in the Western diet (high in fat and simple carbohydrates, low in fibre) compared with a more traditional diet. Here we show that changes in the microbiota of mice consuming a low-MAC diet and harbouring a human microbiota are largely reversible within a single generation. However, over several generations, a low-MAC diet results in a progressive loss of diversity, which is not recoverable after the reintroduction of dietary MACs. To restore the microbiota to its original state requires the administration of missing taxa in combination with dietary MAC consumption. Our data illustrate that taxa driven to low abundance when dietary MACs are scarce are inefficiently transferred to the next generation, and are at increased risk of becoming extinct within an isolated population. As more diseases are linked to the Western microbiota and the microbiota is targeted therapeutically, microbiota reprogramming may need to involve strategies that incorporate dietary MACs as well as taxa not currently present in the Western gut.

/pdf/diet-induced-extinctions-in-the-gut-microbiota-compound-over-aia8thj8t1.pdf

Diet-induced extinctions in the gut microbiota compound over generations

Over the past decade, RNA sequencing (RNA-seq) has become an indispensable tool for transcriptome-wide analysis of differential gene expression and differential splicing of mRNAs. However, as next-generation sequencing technologies have developed, so too has RNA-seq. Now, RNA-seq methods are available for studying many different aspects of RNA biology, including single-cell gene expression, translation (the translatome) and RNA structure (the structurome). Exciting new applications are being explored, such as spatial transcriptomics (spatialomics). Together with new long-read and direct RNA-seq technologies and better computational tools for data analysis, innovations in RNA-seq are contributing to a fuller understanding of RNA biology, from questions such as when and where transcription occurs to the folding and intermolecular interactions that govern RNA function.

RNA sequencing: the teenage years

Carbohydrate-active enzymes (CAZymes) are very important to the biotech industry, particularly the emerging biofuel industry because CAZymes are responsible for the synthesis, degradation and modification of all the carbohydrates on Earth. We have developed a web resource, dbCAN (http://csbl.bmb .uga.edu/dbCAN/annotate.php), to provide a capability for automated CAZyme signature domainbased annotation for any given protein data set (e.g. proteins from a newly sequenced genome) submitted to our server. To accomplish this, we have explicitly defined a signature domain for every CAZyme family, derived based on the CDD (conserved domain database) search and literature curation. We have also constructed a hidden Markov model to represent the signature domain of each CAZyme family. These CAZyme family-specific HMMs are our key contribution and the foundation for the automated CAZyme annotation.

dbCAN: a web resource for automated carbohydrate-active enzyme annotation.

We have recently developed a new version of the DOOR operon database, DOOR 2.0, which is available online at http://csbl.bmb.uga.edu/DOOR/ and will be updated on a regular basis. DOOR 2.0 contains genome-scale operons for 2072 prokaryotes with complete genomes, three times the number of genomes covered in the previous version published in 2009. DOOR 2.0 has a number of new features, compared with its previous version, including (i) more than 250 000 transcription units, experimentally validated or computationally predicted based on RNA-seq data, providing a dynamic functional view of the underlying operons; (ii) an integrated operon-centric data resource that provides not only operons for each covered genome but also their functional and regulatory information such as their cis-regulatory binding sites for transcription initiation and termination, gene expression levels estimated based on RNA-seq data and conservation information across multiple genomes; (iii) a high-performance web service for online operon prediction on user-provided genomic sequences; (iv) an intuitive genome browser to support visualization of user-selected data; and (v) a keywordbased Google-like search engine for finding the needed information intuitively and rapidly in this database.

DOOR 2.0: presenting operons and their functions through dynamic and integrated views.

Reduced dimensionality has long been regarded as an important strategy for increasing thermoelectric performance, for example, in superlattices and other engineered structures. Here we point out and illustrate by examples that three-dimensional bulk materials can be made to behave as if they were two dimensional from the point of view of thermoelectric performance. Implications for the discovery of new practical thermoelectrics are discussed.

High three-dimensional thermoelectric performance from low-dimensional bands.

Motivation Motif identification and analyses are important and have been long-standing computational problems in bioinformatics. Substantial efforts have been made in this field during the past several decades. However, the lack of intuitive and integrative web servers impedes the progress of making effective use of emerging algorithms and tools. Results Here we present an integrated web server, DMINDA 2.0, which contains: (i) five motif prediction and analyses algorithms, including a phylogenetic footprinting framework; (ii) 2125 species with complete genomes to support the above five functions, covering animals, plants and bacteria and (iii) bacterial regulon prediction and visualization. Availability and implementation DMINDA 2.0 is freely available at http://bmbl.sdstate.edu/DMINDA2. Contact qin.ma@sdstate.edu. Supplementary information Supplementary data are available at Bioinformatics online.

/pdf/dminda-2-0-integrated-and-systematic-views-of-regulatory-dna-5geh9g61da.pdf

DMINDA 2.0: integrated and systematic views of regulatory DNA motif identification and analyses

High thermoelectric performance in oxides requires stable conductive materials that have suitable band structures. Here we show, based on an analysis of the thermopower and related properties using first- principles calculations and Boltzmann transport theory in the relaxation time approximation, that hole-doped Cu2O may be such a material. We find that hole- doped Cu2O has a high thermopower of above 200µVK 1 even with doping levels as high as 5.2◊10 20 cm 3 at 500K, mainly attributed to the heavy valence bands of Cu2O. This is reminiscent of the cobaltate family of high-performance oxide thermoelectrics and implies that hole-doped Cu2O could be an excellent thermoelectric material if suitably doped.

https://iopscience.iop.org/article/10.1088/1367-2630/15/4/043029/pdf

Xin Chen

Papers

dbCAN: a web resource for automated carbohydrate-active enzyme annotation.

DOOR 2.0: presenting operons and their functions through dynamic and integrated views.

High three-dimensional thermoelectric performance from low-dimensional bands.

DMINDA 2.0: integrated and systematic views of regulatory DNA motif identification and analyses

Potential thermoelectric performance of hole-doped Cu 2 O