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Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes          P. K. Choudhury (Ph. D, 1st year...
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Methanogenesis• Process of biological production of methane carried out by a  group of strictly Anaerobic Archaea called a...
Methanogenesis from CO2 + H2                               1. CO2     is   activated      by   a                          ...
Biosynthesis of peptidoglycan (part I: biosynthesis of               N-acetylmuramic acid)•   Peptidoglycan (murein) is a ...
Biosynthesis of coenzyme A•   Coenzyme A is an acyl group carrier and plays a central role in    cellular metabolism.•   T...
Heme biosynthesis (part II)•   Heme is a prosthetic group of many important heme proteins,    which are involved in electr...
β-oxidation of fatty acids (Aerobic)•   This pathway depends on aerobic conditions•   Thus, its absense in the list of rel...
Degradation of L-threonine to L-2-amino-acetoacetate    and degradation of L-lysine to crotonyl-CoA•   Degradation of amin...
Biosynthesis of phosphatidylserine and cardiolipin•    Phosphatidylserine and cardiolipin are both components of     biolo...
http://pedant.gsf.de/index.jspPedant3. Database   Annotated Genome sequence and E.C information Uncovering metabolic pathw...
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
http://www.molecular-networks.com/biopath/Biopath.Explore  Reaction and pathway information
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Genomic information  Filtration of Blast hit (0.01) E.C. Blast                                                      t valu...
Metabolic construction: Pathway profile Types of Metabolic Construction 1. Binary Based Metabolic Construction (0 or1) 2. ...
Pathway selection using machine learningUnivariate attribute                    Multivariate attributeSingle attribute (Pa...
Pathway selection using machine learning•   The Filter Method (ReliefF)ReliefF assigns a (relevance) weight to each attrib...
Cross-check by classifiers (by optimizing the attribute weightsfor the cost function) •J48 J48 is based on pruned or unpru...
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
First Step Metabolic Construction • Pedant (Genome Database) • BioPath (Pathway Database)Second Step Pathway Selection    ...
Conclusion1. Relying on functional (metabolic) entities rather than individual genes, this   approach allows for the direc...
Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes   14th Oct, 2011
Uncovering metabolic pathway relevant to phenotypic traits of microbial genomes
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Uncovering metabolic pathway relevant to phenotypic traits of microbial genomes

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Uncovering metabolic pathway relevant to phenotypic traits of microbial genomes

  1. 1. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes P. K. Choudhury (Ph. D, 1st year, Dairy Microbiology)
  2. 2. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  3. 3. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  4. 4. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  5. 5. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  6. 6. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  7. 7. Methanogenesis• Process of biological production of methane carried out by a group of strictly Anaerobic Archaea called as methanogens for ATP generation.• The reduction of CO2 by H2 to form methane (CH4) is a major pathway of methanogenesis and is a forms of anaerobic respiration.• Methanogenesis is a unique series of biochemical reactions that employs novel coenzymes. C1 carriers • Coenzyme methanofuran • Methanopterin • Methyl reductase enzyme complex. Redox Coenzymes • Coenzymes F420 and 7-mercaptoheptanoylthreonine phosphate( coenzyme B-CoB), • Methyl reductase enzyme complex.
  8. 8. Methanogenesis from CO2 + H2 1. CO2 is activated by a methanofuran-containing enzyme and reduced to the formyl level. 2. The formyl group is transferred to methanopterin. It is subsequently dehydrated and reduced in two separate steps to the methylene and methyl levels. 3. The methyl group is transferred from methanopterin to enzyme containing CoM by the enzyme methyl transferase. Methyl-CoM is reduced to methane by methyl reductase.
  9. 9. Biosynthesis of peptidoglycan (part I: biosynthesis of N-acetylmuramic acid)• Peptidoglycan (murein) is a cell wall polymer common to most eubacteria. In the first phase of its biosynthesis N- acetylmuramate is formed.• Members of the domain archaea lack peptidoglycan in their cell wall (pseudopeptidoglycan).• Instead of N-acetylmuramicacid, pseudomurein contains N- acetyltalosaminuronic acid (the biosynthetic pathway of N- acetyltalosaminuronic acid).• The relevance of the N-acetylmuramic acid pathway in distinguishing methanogens from non-methanogens presumably represents the differences in cell wall composition of archaea compared to eubacteria and identifies methanogens as archaebacteria.
  10. 10. Biosynthesis of coenzyme A• Coenzyme A is an acyl group carrier and plays a central role in cellular metabolism.• The biosynthetic pathway biosynthesis of coenzyme A (coa1) includes both the biosynthesis of coenzyme A from pantothenate and the de novo synthesis of pantothenate.• In several non-methanogenic archaea, the set of enzymes for the synthesis of pantothenate is conserved with the corresponding bacterial or eukaryotic enzymes.• In methanogenic archaea, enzymes for the synthesis of pantothenate lacks. Thus, autotrophic methanogens follow a unique pathway for de novo biosynthesis of coenzyme A.
  11. 11. Heme biosynthesis (part II)• Heme is a prosthetic group of many important heme proteins, which are involved in electron transfer or gas transport.• Heme proteins such as cytochromes a, b, and c and catalase are also known for archaea. For the first part of heme synthesis from delta-aminolevulinic acid to uroporphyrinogen III, the homologs of the corresponding eukaryotic and bacterial enzymes are present in many archaea.• But for the conversion of uroporphyrinogen III to protoheme, is absent in archaea .• The relevance of this pathway for the phenotype methanogenesis’ presumably arises from the fact that all methanogens known so far are members of the archaea domain.
  12. 12. β-oxidation of fatty acids (Aerobic)• This pathway depends on aerobic conditions• Thus, its absense in the list of relevant pathways may refer to the anaerobic lifestyle of methanogens.• Distinguishing obligate anaerobes and obligate aerobes also support this assumption, as the pathway of β-oxidation of fatty acids is one of the most relevant pathways for this phenotype.
  13. 13. Degradation of L-threonine to L-2-amino-acetoacetate and degradation of L-lysine to crotonyl-CoA• Degradation of amino acids can be used either to gain energy or to generate fatty acids. Both degradation pathways, are not operative in methanogens.• In some anaerobic microorganisms, degradation of several amino acids is coupled to methanogens by a syntrophic relationship: hydrogen, which is produced by the oxidation of the amino acid in the degrading organism, is consumed in methanogenesis by the methanogenic organism.• Thus, looking at these degradation processes presumably helps to distinguish methanogens from other anaerobic genomes.
  14. 14. Biosynthesis of phosphatidylserine and cardiolipin• Phosphatidylserine and cardiolipin are both components of biological membranes. Differences in membrane lipids led to the distinction of the domain of archaea from the domain of bacteria• Composition and biosynthetic pathways of polar lipids in methanogens differ from those of other groups of archaea.• Among the archaea, phospholipids with amino groups, such as phosphatidylserine, only occur in methanogens and some related Euryarchaeota.
  15. 15. http://pedant.gsf.de/index.jspPedant3. Database Annotated Genome sequence and E.C information Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  16. 16. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  17. 17. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  18. 18. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  19. 19. http://www.molecular-networks.com/biopath/Biopath.Explore Reaction and pathway information
  20. 20. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  21. 21. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  22. 22. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  23. 23. Genomic information Filtration of Blast hit (0.01) E.C. Blast t value=12Phenotypic information 1. National Centre for Biotechnology information 2. EBI Intregated database 3. Karyns genomes (Presence and absence of phenotypic traits)
  24. 24. Metabolic construction: Pathway profile Types of Metabolic Construction 1. Binary Based Metabolic Construction (0 or1) 2. Score based Metabolic construction . (Score (P) = 0.0-1.0) ≤ 0.5 predicted presence of pathway ≥ 0.5 predicted absence of pathway
  25. 25. Pathway selection using machine learningUnivariate attribute Multivariate attributeSingle attribute (Pathway) evaluation Multiple attribute (Pathway) evaluation • The Filter Methid • The embedded method • Wrapper method
  26. 26. Pathway selection using machine learning• The Filter Method (ReliefF)ReliefF assigns a (relevance) weight to each attribute according to how well theirvalues distinguish among instances of different classes and according to how wellthey cluster instances of the same class and the nearest instances belonging toother classes are determined.• The Embedded Method (SVMAttributeEval)SVMAttributeEval combines a (linear) Support Vector Machine (SVM) and thetechnique of Recursive Feature Elimination (RFE) in order to assess the relevance ofattribute subsets. RFE is an iterative process of training a classifier computing theattribute ranking criterion for each attribute and removing the attribute with thesmallest ranking criterion.• Wrapper method (naïve Bayes classifier)Wrappers train a classifier based on an attribute subset and score the predictivepower of the subset by cross-validation. An exhaustive search for the best subsetamong all possible attribute subsets is very complex due to the high number ofpossible subsets.
  27. 27. Cross-check by classifiers (by optimizing the attribute weightsfor the cost function) •J48 J48 is based on pruned or unpruned C 4.5 decision trees learned by the algorithm. C4.5 splits the input data into smaller subsets by iteratively choosing individual attributes for the decision based on their information gain. • IB1 IB1 is a nearest neighbor classifier based on normalized Euclidean distance. The class of its nearest neighbor is assigned to an instance. Naïve Bayes is a probabilistic classifier that applies a simplification of Bayes law by (naïvely) assuming the independence of attributes. Prior probability and likelihood are estimated by the corresponding frequencies in the training data. •SMO SMO implements the sequential minimal optimization algorithm for training a SVM. A SVM is looking for a hyperplane that is an optimal boundary between the classes (that is, a boundary that maximizes the surrounding margin containing no instance). The model is represented by socalled support vectors, a small set of instances that are sufficient to determine the boundary. If linear separation is not possible, the data can be transformed to a higher dimensional space by so-called kernel functions in order to allow linear separation. • naïve Bayes
  28. 28. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  29. 29. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  30. 30. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  31. 31. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  32. 32. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  33. 33. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  34. 34. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  35. 35. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  36. 36. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  37. 37. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  38. 38. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  39. 39. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  40. 40. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  41. 41. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  42. 42. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  43. 43. First Step Metabolic Construction • Pedant (Genome Database) • BioPath (Pathway Database)Second Step Pathway Selection • Pathway profile • Phenotypic DataThird step Cross Validation • Attribute selection algorithms • Classifier Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  44. 44. Conclusion1. Relying on functional (metabolic) entities rather than individual genes, this approach allows for the direct generation of hypotheses about the biochemical basis of phenotypic traits.2. This method is based on the completely automated analysis of genome data. It is generic and thus applicable to any phenotype and to thousands of genomes yet to be sequenced as a result of high-throughput sequencing technologies.3. This also includes species and phenotypes whose biochemistry is largely unknown so far. The number of species that are not accessible by experiments due to their life style but for which the genomic sequence is available will also grow enormously in the next years.4. Thus, the automatic linking of phenotypes to associated metabolic processes, as provided by this method, will be highly valuable for the interpretation of genome information. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011
  45. 45. Uncovering metabolic pathways relevant to phenotypic traits of microbial genomes 14th Oct, 2011

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