Homology Profile-HMMs Domains Protein-family Databases How to build a new (Pfam) protein family EMBO...
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Transcript of Homology Profile-HMMs Domains Protein-family Databases How to build a new (Pfam) protein family EMBO...
- Slide 1
- Homology Profile-HMMs Domains Protein-family Databases How to build a new (Pfam) protein family EMBO Workshop, Cape Town, 2014 Function annotation transfer Outline Pfam database
- Slide 2
- Homology EMBO Workshop, Cape Town, 2014
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- Definition: Two proteins are homologous if they share a common ancestor, i.e. they are evolutionary related EMBO Workshop, Cape Town, 2014
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- Symmetric A A B B homologous Transitive B B A A homologous A A B B AND B B C C homologous A A C C
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- Detecting homology EMBO Workshop, Cape Town, 2014
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- Human: 1 MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDEMKASE 60 MGLSDGEWQLVLNVWGKVEAD GHGQEVLI LFK HPETL KFDKFK LKSE MK SE Mouse: 1 MGLSDGEWQLVLNVWGKVEADLAGHGQEVLIGLFKTHPETLDKFDKFKNLKSEEDMKGSE 60 Human: 61 DLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQVLQSKH 120 DLKKHG TVLTALG ILKKKG H AEI PLAQSHATKHKIPVKYLEFISE II VL H Mouse: 61 DLKKHGCTVLTALGTILKKKGQHAAEIQPLAQSHATKHKIPVKYLEFISEIIIEVLKKRH 120 Human: 121 PGDFGADAQGAMNKALELFRKDMASNYKELGFQG 154 GDFGADAQGAM KALELFR D A YKELGFQG Mouse: 121 SGDFGADAQGAMSKALELFRNDIAAKYKELGFQG 154 By excess similarity (see Pearson Curr Protoc Bioinformatics 2013 ) Statistical significance (e.g. E-values) Sequence similarity EMBO Workshop, Cape Town, 2014
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- 2G2X: 1 MAYWLMKSEPDELSIEALARLGEARWDGVRNYQARNFLRAMSVGDEFFFYH-----SSCP 55 MAYWL D W Y N VGD Y 2P5D: 4 MAYWLCITNEDNWKVIKEKKI----WGVAERY--KNTINKVKVGDKLIIYEIQRSGKDYK 57 2G2X: 56 QPGIAGIARITRAAYPD------PTALDPESHY 82 P I G Y D PT P 2P5D: 58 PPYIRGVYEVVSEVYKDSSKIFKPTPRNPNEKF 90 Excess sequence similarity? Structural similarity EMBO Workshop, Cape Town, 2014
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- 2G2X 2P5D Structural similarity EMBO Workshop, Cape Town, 2014
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- Structural similarity 2G2X 2P5D
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- Structural similarity 2G2X 2P5D Z-score = 12.2 RMSD = 2.9 Lali = 122 %id =20 DALI: http://ekhidna.biocenter.helsinki.fi/dali_lite/start
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- http://www.microbesonline.org EMBO Workshop, Cape Town, 2014 Genomic context See e.g. Jun et al. BMC Genomics 2009
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- http://www.microbesonline.org EMBO Workshop, Cape Town, 2014 Genomic context Homology See e.g. Jun et al. BMC Genomics 2009
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- http://www.microbesonline.org EMBO Workshop, Cape Town, 2014 Genomic context See e.g. Jun et al. BMC Genomics 2009 Homology?
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- http://www.microbesonline.org EMBO Workshop, Cape Town, 2014 Genomic context Mostly used for distinguishing orthology from paralogy
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- Origins of homology in proteins EMBO Workshop, Cape Town, 2014
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- Origin of homology in proteins Speciation (orthology) Gene duplication (paralogy) Horizontal gene transfer (xenology) Whole genome duplication (ohnology) Gametology EMBO Workshop, Cape Town, 2014
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- Myoglobin: Serves as a reserve supply of oxygen and facilitates the movement of oxygen within muscles. Orthology EMBO Workshop, Cape Town, 2014
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- Speciation (orthology) Gene duplication (paralogy) Horizontal gene transfer (xenology) Whole genome duplication (ohnology) Gametology Origin of protein homology EMBO Workshop, Cape Town, 2014
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- Myoglobin: Serves as a reserve supply of oxygen and facilitates the movement of oxygen within muscles. Hemoglobin: Oxygen-transport protein in red-blood cells of vertebrates Paralogy
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- EMBO Workshop, Cape Town, 2014
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- Ancestral Globin B C Myo A Hemo EMBO Workshop, Cape Town, 2014
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- Ancestral Globin B C Myo A Hemo EMBO Workshop, Cape Town, 2014
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- Ancestral Globin B C Myo A Hemo Myo Hemo Myo Hemo EMBO Workshop, Cape Town, 2014
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- Origin of protein homology EMBO Workshop, Cape Town, 2014 Speciation (orthology) Gene duplication (paralogy) Horizontal gene transfer (xenology) Whole genome duplication (ohnology) Gametology, Synology
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- Mindell and Meyer Trends in Ecology and Evolution 2001
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- EMBO Workshop, Cape Town, 2014 Homology: why bother? Slide courtesy of Alex Mitchell (EMBL-EBI)
- Slide 27
- Homology Function? Structure (homology modeling) EMBO Workshop, Cape Town, 2014 Homology: why bother?
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- Schubert et al. Nat. Struct. Biol. 5 (1998) Protein function(s) EMBO Workshop, Cape Town, 2014
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- A way to capture biological knowledge in a written and computable form A set of concepts and their relationships to each other www.ebi.ac.uk/QuickGO EMBO Workshop, Cape Town, 2014 Slide courtesy of Alex Mitchell (EMBL-EBI) The Gene Ontology (GO)
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- 1. Molecular Function 2. Biological Process 3. Cellular Component An elemental activity or task or job protein kinase activity insulin receptor activity A commonly recognised series of events cell division Where a gene product is located mitochondrion mitochondrial matrix mitochondrial inner membrane EMBO Workshop, Cape Town, 2014 Slide courtesy of Alex Mitchell (EMBL-EBI) GO: 3 ontologies in 1
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- Protein Families EMBO Workshop, Cape Town, 2014
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- http://www.studyblue.com/notes/note/n/exam-3/deck/8955883 Globins in Human
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- Definition: We call family a group of evolutionary related proteins or protein regions EMBO Workshop, Cape Town, 2014
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- P P A A Why protein families?
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- Human: 1 MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDEMKASE 60 MGLSDGEWQLVLNVWGKVEAD GHGQEVLI LFK HPETL KFDKFK LKSE MK SE Mouse: 1 MGLSDGEWQLVLNVWGKVEADLAGHGQEVLIGLFKTHPETLDKFDKFKNLKSEEDMKGSE 60 Human: 61 DLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQVLQSKH 120 DLKKHG TVLTALG ILKKKG H AEI PLAQSHATKHKIPVKYLEFISE II VL H Mouse: 61 DLKKHGCTVLTALGTILKKKGQHAAEIQPLAQSHATKHKIPVKYLEFISEIIIEVLKKRH 120 Human: 121 PGDFGADAQGAMNKALELFRKDMASNYKELGFQG 154 GDFGADAQGAM KALELFR D A YKELGFQG Mouse: 121 SGDFGADAQGAMSKALELFRNDIAAKYKELGFQG 154 Why protein families? EMBO Workshop, Cape Town, 2014
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- Human: 1 MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDEMKASE 60 MGLSDGEWQLVLNVWGKVEAD GHGQEVLI LFK HPETL KFDKFK LKSE MK SE Mouse: 1 MGLSDGEWQLVLNVWGKVEADLAGHGQEVLIGLFKTHPETLDKFDKFKNLKSEEDMKGSE 60 Human: 61 DLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQVLQSKH 120 DLKKHG TVLTALG ILKKKG H AEI PLAQSHATKHKIPVKYLEFISE II VL H Mouse: 61 DLKKHGCTVLTALGTILKKKGQHAAEIQPLAQSHATKHKIPVKYLEFISEIIIEVLKKRH 120 Human: 121 PGDFGADAQGAMNKALELFRKDMASNYKELGFQG 154 GDFGADAQGAM KALELFR D A YKELGFQG Mouse: 121 SGDFGADAQGAMSKALELFRNDIAAKYKELGFQG 154 Why protein families? EMBO Workshop, Cape Town, 2014
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- P P A A B B H H G G E E C C D D F F
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- We can detect functionally important residues EMBO Workshop, Cape Town, 2014
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- We can detect functionally important residues EMBO Workshop, Cape Town, 2014
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- We have a window open on evolutionary diversity Human: 1 MGLSDGEWQLVLNVWGKVEADIPGHGQEVLIRLFKGHPETLEKFDKFKHLKSEDEMKASE 60 MGLSDGEWQLVLNVWGKVEAD GHGQEVLI LFK HPETL KFDKFK LKSE MK SE Mouse: 1 MGLSDGEWQLVLNVWGKVEADLAGHGQEVLIGLFKTHPETLDKFDKFKNLKSEEDMKGSE 60 Human: 61 DLKKHGATVLTALGGILKKKGHHEAEIKPLAQSHATKHKIPVKYLEFISECIIQVLQSKH 120 DLKKHG TVLTALG ILKKKG H AEI PLAQSHATKHKIPVKYLEFISE II VL H Mouse: 61 DLKKHGCTVLTALGTILKKKGQHAAEIQPLAQSHATKHKIPVKYLEFISEIIIEVLKKRH 120 Human: 121 PGDFGADAQGAMNKALELFRKDMASNYKELGFQG 154 GDFGADAQGAM KALELFR D A YKELGFQG Mouse: 121 SGDFGADAQGAMSKALELFRNDIAAKYKELGFQG 154 EMBO Workshop, Cape Town, 2014
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- We have a window open on evolutionary diversity
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- Example (using homology for protein annotation) EMBO Workshop, Cape Town, 2014
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- H. influenzae protein (3M71) 1.20 Chen et al. Nature 467 (2010) TUM, January 2013 EMBO Workshop, Cape Town, 2014 New York Consortium on Membrane Protein Structure (NYCOMPS)
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- TUM, January 2013
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- Thomine and Barbier-Brygoo Nature 467:1058-59 (2010) EMBO Workshop, Cape Town, 2014
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- Thomine and Barbier-Brygoo Nature 467:1058-59 (2010) EMBO Workshop, Cape Town, 2014
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- Chen et al. Nature 467 (2010)
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- EMBO Workshop, Cape Town, 2014 Chen et al. Nature 467 (2010)
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- EMBO Workshop, Cape Town, 2014 Chen et al. Nature 467 (2010)
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- TUM, January 2013
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- EMBO Workshop, Cape Town, 2014 OPEN Jalview 1. 2. File -> Input Alignment -> From File PF03595_seed.txt
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- EMBO Workshop, Cape Town, 2014 Colour -> BLOSUM62 1.
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- EMBO Workshop, Cape Town, 2014 OPEN Chimera 1. File -> Open 3M71.pdb 2.
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- EMBO Workshop, Cape Town, 2014
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- out
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- EMBO Workshop, Cape Town, 2014 Actions -> Atoms/Bonds -> wire 1. Actions -> Atoms/Bonds -> show 2.
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- out EMBO Workshop, Cape Town, 2014 Actions -> Atoms/Bonds -> wire 1. Actions -> Atoms/Bonds -> show 2.