Friday, 7 August 2015

Useful information for a computational biologist

If you want to be a computational biologist then you must read the article mentioned below. The article has covered the role of computational biologist, the approach before starting a project, use of software's, pipelines and scripts, and the most important thing is: "think like a Scientist not like a programmer/coder.  Interesting and must read.
http://www.nature.com/nbt/journal/v31/n11/full/nbt.2740.html 

Monday, 11 May 2015

Emerging interest towards the understanding of xenobiotics metabolism by gut microbes

From the last few years, researchers started thinking in this direction also. As all of the xenobiotics, we took daily either directly (pharmaceutical drugs) or indirectly (from our regular diet) first encountered by microbes residing in our gut. In our gut, microbes are present in larger number in comparison to our own cells so it is obvious that they might have key enzymes also for the metabolism of xenobiotics. This early stage metabolism (before reaching into blood circulation) might affect overall metabolism by the host. Researcher in this field Carmody and Turnbaugh described in detail that microbial enzymes are involved in the metabolism of xenobiotics compounds either directly or indirectly (active or deactivate host enzyme via microbial metabolite). You can read this paper from the following link http://www.jci.org/articles/view/72335. They highlighted till now known examples of xenobiotics metabolism by gut microbes and effect of this metabolism on overall efficacy and toxicity of the compounds. In 1998 around two decades ago first time Okuda et al discussed probable mechanism responsible for the deaths of eighteen patients treated with soravudine and oral 5-fluorouracil prodrugs. You can read this paper from the following link http://www.ncbi.nlm.nih.gov/pubmed/9808711. They addressed how the metabolite produced by the gut microbes involved in the inhibition of key enzyme (hepatic dihydropyrimidine dehydrogenase) that are responsible for maintaining the level of 5-FU. This is the only one example which I have mentioned here, there could be several others, we have a very limited information of microbial metabolism of xenobiotics. But, now, because of next generation sequencing  and metagenomics, the understanding towards the microbial world is increasing day by day. Now a days this microbial metabolism part is important to study in order to develop better pharmaceuticals (increased efficacy and/or decrease toxicity). Hopefully, Recently completed project like Human microbiome project (http://hmpdacc.org/) could provide new directions to this field.
Here I am sharing a recently published note on “Why xenobiotics, foreign chemicals to our bodies, are the next frontier in health and disease.”

Thursday, 7 May 2015

Role of Gut Microbiome in the Regulation of Host Metabolism

Microbes are integral part of our routine life as they live in a constant association with the host to regulate the metabolism. Collection of microbes present at the epithelial surface and cavities of our body such as stomach are known as human associated microbiome/microflora. Bacteria are the predominant part of the microflora, however, some amount of virus, fungi and protozoans also present. The most complex community ever studied is the human distal gut microbiome, which contained 1,000 different microbial species across human populations. These microbes contain millions of different genes, largely more than the total number of host genes. Now a days, several research groups are working on how gut dysbiosis is related with the various metabolic disorders such as obesity, diabetes, IBD, cancer etc. This is quite interesting filed to know how microbes are interacting with each other or with the host in order to attain healthy or diseased phenotype. Since, the microflora is very complex and dynamic, and it is known to have a profound influence on the human metabolism. This vast diversity of the human-associated microbes poses a big challenge in the field of medical science. 
Recently, an interesting report published on the following topic "Modern Life Depletes Your Gut Microbes in a Number of Different Ways". 

Tuesday, 14 April 2015

Woods: A fast and accurate functional annotator and classifier of genomic and metagenomic sequences

Time to analyse your data using woods "a functional annotator and classifier of genomic and metagenomic sequences"
A recent publication out from our lab. Please explore and write back to (ashok@iiserb.ac.in) in case of any problem. Comments are welcome. 

Databases and tools for understanding the xenobiotics metabolism

Human physiology influenced by human microbiome in several ways, mainly via impact of human gut microbes on the metabolism of xenobiotic compounds. These interactions are quite important as they are very significant in order to improve overall efficacy of therapeutic compounds, but microbial metabolism of xenobiotics still remains unexplored. Here, I have provided the link of important databases and tools for biotransformation/degradation of xenobiotics. 

1. The Transformer database: biotransformation of xenobiotics
2. UM-BBD -- University of Minnesota Biocatalysis/Biodegradation Database
3. Eawag: Biocatalytic/Biodegradation database, to identify the metabolic enzyme for candidate drug
4. Gut Pharmacomicrobiomics: the tip of an iceberg of complex interactions between drugs and gut-associated microbes
http://www.gutpathogens.com/content/4/1/16
5. DrugBank 4.0: shedding new light on drug metabolism

Wednesday, 8 April 2015

Gut Pharmacomicrobiomics:

To study the influence of gut microbes on xenobiotics metabolism.

Pharmacomicrobiomics database:
The PharmacoMicrobiomics web portal is a part of an initiative to explore the interactions between human-associated microbes (human microbiome) and drugs by building a knowledgebase that allows interested students and investigators "to predict the behavior of untested members of drug classes or unstudied microbial species, and to design laboratory experiments for testing these predictions.

Available at: http://www.biomedcentral.com/1471-2105/12/S7/A10

http://pharmacomicrobiomics.com/

Thursday, 19 March 2015

Composition based methods for taxonomic classification

Taxonomic classification of 16S rRNA or metagenomic sequencing reads is one of the most important steps in order to understand the diversity of microbes within a microbial community. Methods for taxonomic classification have been divided into two major categories, based on their algorithms, composition based methods and similarity-based methods. Here, I have discussed in detail about composition based methods. Most probably in my next post, I would like to focus on similarity-based approaches. 

1. TETRA: a web-service and a stand-alone program for the analysis and comparison of tetranucleotide usage patterns in DNA sequences.

ETRA provides a statistical analysis of tetranucleotide usage patterns in genomic fragments, either via a web-service or a stand-alone program.

2. PhyloPathia: Accurate phylogenetic classification of variable-length DNA fragments.
PhyloPythia, a composition-based classifier that combines higher-level generic clades from a set of 340 completed genomes with sample-derived population models. Extensive analyses on synthetic and real metagenome data sets showed that PhyloPythia allows the accurate classification of most sequence fragments across all considered taxonomic ranks, even for unknown organisms.
Available at:
http://cbcsrv.watson.ibm.com/phylopythia.html

3. PhyloPathiaS: The PhyloPythiaS Web Server for Taxonomic Assignment of Metagenome Sequences.
PhyloPythiaS is a fast and accurate sequence composition-based classifier that utilizes the hierarchical relationships between clade. PhyloPythiaS is freely available for non-commercial users and can be installed on a Linux-based machine.

4. TACOA: Taxonomic classification of environmental genomic fragments using a kernelized nearest neighbor approach
The classifier combines the idea of the k-nearest neighbor with strategies from kernel-based learning. It is an accurate multi-class taxonomic classifier for environmental genomic fragments. TACOA can predict with high reliability the taxonomic origin of genomic fragments as short as 800 bp.
http://www.biomedcentral.com/1471-2105/10/56#B20

5. RAIphy: Phylogenetic classification of metagenomics samples using iterative refinement of relative abundance index profiles
RAIphy is a composition-based semisupervised binning algorithm that uses a novel sequence similarity metric with iterative refinement of taxonomic models and functions effectively. RAIphy has been implemented as a simple, compact standalone desktop application, which is fast compared to similarity-search-based applications. While achieving competitive binning accuracies for the DNA sequencing read length range (100-1000 bp), the method also performs accurately for longer environmental contigs.

6. NBC: the Naive Bayes Classification tool webserver for taxonomic classification of metagenomic reads.
A webserver that implements the naïve Bayes classifier (NBC) to classify all metagenomic reads to their best taxonomic match. Results indicate that NBC can assign next-generation sequencing reads to their taxonomic classification and can find significant populations of genera that other classifiers may miss.

7. Phymm and PhymmBL: Metagenomic Phylogenetic Classification with Interpolated Markov Models

Phymm, a classifier for metagenomic data, that has been trained on 539 complete, curated genomes and can accurately classify reads as short as 100 bp, representing a substantial leap forward over previous composition-based classification methods. They also describe how combining Phymm with sequence alignment algorithms, further improves accuracy.

8. GSTaxClassifier: a genomic signature based taxonomic classifier for metagenomic data analysis.
GSTaxClassifier takes input nucleotide sequences and using a modified Bayesian model evaluates the genomic signatures between metagenomic query sequences and reference genome databases. The simulation studies of a numerical data sets showed that GSTaxClassifier could serve as a useful program for metagenomics studies.

9. SPHINX: an algorithm for taxonomic binning of metagenomic sequences.
A hybrid binning approach (SPHINX) that achieves high binning efficiency by utilizing the principles of both 'composition'- and 'alignment'-based binning algorithms.

10. TAC-ELM: Metagenomic taxonomic classification using extreme learning machines.
A new sequence composition-based taxonomic classifier using extreme learning machines referred to as TAC-ELM for metagenomic analysis. TAC-ELM uses the framework of extreme learning machines to quickly and accurately learn the weights for a neural network model. The input features consist of GC content and oligonucleotides.

11. AKE - the Accelerated k-mer Exploration web-tool for rapid taxonomic classification and visualization
Acceleration in AKE’s taxonomic assignments is achieved by a special machine learning architecture, which is well suited to model data collections that are intrinsically hierarchical. 

12. TAXSOM: Practical application of self-organizing maps to interrelate biodiversity and functional data in NGS-based metagenomics.
Biodiversity is usually targeted by classifying 16S ribosomal RNA genes, while metagenomic approaches target metabolic genes. However, both approaches remain isolated, as long as the taxonomic and functional information cannot be interrelated. Techniques like self-organizing maps (SOMs) have been applied to cluster metagenomes into taxon-specific bins in order to link biodiversity with functions.

13. Kraken: ultrafast metagenomic sequence classification using exact alignments

Kraken is an ultrafast and highly accurate program for assigning taxonomic labels to metagenomic DNA sequences. Using exact alignment of k-mers, Kraken achieves classification accuracy comparable to the fastest BLAST program. 

14. RDP Classifier: Naive Bayesian classifier for rapid assignment of rRNAsequences into the new bacterial taxonomy.

The Ribosomal Database Project (RDP) Classifier, a naïve Bayesian classifier, can rapidly and accurately classify bacterial 16S rRNA sequences into the new higher-order taxonomy proposed in Bergey's Taxonomic Outline of the Prokaryote. For shorter rRNA segments, such as those that might be generated by pyrosequencing, the error rate varied greatly over the length of the 16S rRNA gene. The RDPClassifier is suitable both for the analysis of single rRNA sequences and for the analysis of libraries of thousands of sequences.
Available at: http://rdp.cme.msu.edu/

15. 16S Classifier: A Tool for Fast and Accurate Taxonomic Classification of 16S rRNA Hypervariable Regions in Metagenomic Datasets

16S Classifier is developed using a machine learning method, Random Forest, for faster and accurate taxonomic classification of short hypervariable regions of 16S rRNA sequence. It displayed precision values of up to 0.91 on training datasets and the precision values of up to 0.98 on the test dataset. On real metagenomic datasets, it showed up to 99.7% accuracy at the phylum level and up to 99.0% accuracy at the genus level.