From: Peter R. <pet...@ch...> - 2010-03-12 16:36:10
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Paul Schofield wrote: > The phenotype is the result of an alk phos assay. This is not a > measure of the amount of protein present. If you want to state that > the enzyme concentration is increased then quantitative immunoassay is > required. This is generally not done. The increase in activity IMPLIES > that the enzyme is present in increased quantity but this is only an > implication without evidence. It could be the result of an allosteric > activation, removal of an inhibitor, proteolytic processing, > modification etc etc. We only happen to know that its most often due > to leakage from normally closed compartments. > > > There could logically be two terms "Increased concentration of > alkaline phosphatase ( whatever variant)" as measured by an assay that > measures the amount of this specific protein > > and > > Increased alkaline phosphatase activity which can IMPLY that there has > been mislocalisation of the protein but does not rely on direct > protein measurements > > > This is a bit similar to the discussion we have had before on the good > old hypospadias. Do you define these as the displacement of an orifice > - ie what you observe, or by the aberrant process you know gave rise > to it. We agreed that as we are describing phenotypes then we just > describe what is measured or observed and with most normal clinical > measurements of alk phos this is an activity measurement rather than > quantitative isozyme specific immunoassay. > > > My six penn'orth > Yes, but I think on the other hand we should not disregard medical information or knowledge in those cases where we are at least very sure of ourselves. By this I mean that it would be certainly wrong to write a PATO definition of halucinations as, say, "abnormal brain activity resulting from too much serotonin", there are cases where we do in fact know more than just the "mere" observation. Observing an increased level of bone isoforms of AP simply does not mean that there is an increased activity of bone-AP that is otherwise normally in serum, and if we are going to use the information for inference then we should not discard this information. Obviously, the art of this consists in getting the grey zone right! My 2c :-0} Peter > > > !! > > P. > > > > On 12 Mar 2010, at 16:13, Peter Robinson wrote: > >> Chris Mungall wrote: >>> wrong quality >>> >>> option 1: use an anonymous class / post-composition for the bearer >>> 'increased rate' and inheres_in some ('alkaline phosphotase activity' >>> and has_catalyst some 'alkaline phosphatase, placental') >> >> >> >> It is not the activity itself that is abnormal, i.e., the individual >> enzymes are abnormal. It is that fact that alk phos is being leaked >> into >> the blood circulation at an abnormally high rate. This means that we >> measure an increased alk phos activity, but the actual phenomenon is >> that alk phos activity is present in the "wrong" place, i.e., in the >> blood stream. >> >> -Peter >> >> >> >> >> >> >> >> >> >> >> >>> option 2: request the more specific term of GO >>> >>> On Mar 12, 2010, at 6:21 AM, George Gkoutos wrote: >>> >>>> Oh I see - many apologies, you guys are both right then. >>>> >>>> >>>> so, we have to go with post-composing the term (and check if GO >>>> might >>>> consider adding it) >>>> >>>> so something like >>>> >>>> PATO:increased >>>> inheres_in: GO:alkaline phosphatase activity >>>> has_central_participant: PRO:000003969 ! alkaline phosphatase, >>>> placental >>>> >>>> >>>> >>>> >>>> On 12 Mar 2010, at 13:57, Paul Schofield wrote: >>>> >>>>> Its not increased concentration of alkaline phosphatase that being >>>>> measured George, its activity. Surely therefore as long as the >>>>> "intersection_of:towards" works here it should be something like: >>>>> >>>>> >>>>>>> PATO:increased >>>>>>> GO:alkaline phosphatase activity >>>>>>> inhering in: FMA serum >>>>>> intersection_of: towards PRO:000003969 ! alkaline phosphatase, >>>>>> placental type >>>>> Syntax not my forte! >>>>> >>>>> >>>>> P. >>>>> >>>>> >>>>> >>>>> On 12 Mar 2010, at 13:50, George Gkoutos wrote: >>>>> >>>>>> On 12 Mar 2010, at 09:16, Peter Robinson wrote: >>>>>> >>>>>>> Dr. med. Sandra Dölken wrote: >>>>>>>> I added those terms while doing an annotation and have been >>>>>>>> discussing >>>>>>>> this with some people from clinical chemistry and with George as >>>>>>>> well for >>>>>>>> the decomposition. >>>>>>>> >>>>>>>> There are a number of Isozymes of the Alkaline Phosphatase, >>>>>>>> trying to >>>>>>>> clarify some of the points from below: >>>>>>> >>>>>>> I think we would need to say in PATO >>>>>>> >>>>>>> PATO:increased >>>>>>> GO:alkaline phosphatase activity >>>>>>> inhering in: FMA serum >>>>>>> ???:originating_from FMA placenta >>>>>>> ???:corresponding to: PRO:Isozyme placental AP >>>>>>> >>>>>>> Or something along these lines. >>>>>> Hi Peter, >>>>>> >>>>>> Sandra and I have provided definitions for this some time back for >>>>>> example: >>>>>> >>>>>> [Term] >>>>>> id: HP:0010682 ! Elevated placental alkaline phosphatase >>>>>> intersection_of: PATO:0001162 ! increased concentration >>>>>> intersection_of: towards PRO:000003969 ! alkaline phosphatase, >>>>>> placental type >>>>>> >>>>>> >>>>>> I think that should be sufficient for the observable here but like >>>>>> Paul points out it does not discriminate between enzyme levels and >>>>>> activity upregulation. We could possible add something like >>>>>> results_from ... >>>>>> >>>>>> >>>>>> George >>>>>> >>>>>> >>>>>>> -peter >>>>>>> >>>>>>>> 1) Elevated placental alkaline phosphatase: >>>>>>>> PATO:increased_rate of >>>>>>>> GO:alkaline phosphatase activity and occurs_in placenta: >>>>>>>> -> That is a bit dodgy. Not the activity in the placenta but the >>>>>>>> production of AP by the placenta is increased. >>>>>>>> >>>>>>>> 2) Tissue non-specific alkaline phosphatase: has a number of >>>>>>>> differend >>>>>>>> subset for example "of bone origin", "of hepatic origin"... >>>>>>>> -> we are talking about the same isozyme which is produced in >>>>>>>> the >>>>>>>> liver >>>>>>>> and in the bone... >>>>>>>> -> the prefixes "low" or "increased" mean that production of the >>>>>>>> AP in >>>>>>>> question is either raised or lowered, which might be due to for >>>>>>>> example >>>>>>>> certain liver or bone diseases. >>>>>>>> >>>>>>>> -Sandra >>>>>>>> >>>>>>>> >>>>>>>>> I see a few new bulk additions such as >>>>>>>>> >>>>>>>>> is_a HP:0000118 ! Organ abnormality >>>>>>>>> is_a HP:0001939 ! Metabolism abnormality >>>>>>>>> is_a HP:0004379 ! Abnormality of alkaline phosphatase >>>>>>>>> metabolism >>>>>>>>> is_a HP:0003155 ! Elevated alkaline phosphatase >>>>>>>>> is_a HP:0010682 ! Elevated placental alkaline phosphatase >>>>>>>>> *** >>>>>>>>> >>>>>>>>> in Obol I'll treat these as PATO:increased_rate of GO:alkaline >>>>>>>>> phosphatase activity and occurs_in placenta >>>>>>>>> >>>>>>>>> or perhaps not... >>>>>>>>> >>>>>>>>> less sure of: >>>>>>>>> >>>>>>>>> is_a HP:0004379 ! Abnormality of alkaline phosphatase >>>>>>>>> metabolism >>>>>>>>> is_a HP:0003282 ! Low alkaline phosphatase >>>>>>>>> is_a HP:0010683 ! Low tissue non-specific alkaline >>>>>>>>> phosphatase >>>>>>>>> is_a HP:0010684 ! Low alkaline phosphatase of bone origin >>>>>>>>> *** >>>>>>>>> >>>>>>>>> how do we deal with specificity? GO term request? or PRO >>>>>>>>> request >>>>>>>>> for >>>>>>>>> ALPL? >>>>>>>>> >>>>>>>>> what about bone origin? is this just indicating the specific >>>>>>>>> gene >>>>>>>>> involved? PRO may be best here. >>>>>>>>> >>>>>>>>> Will HPO pre-compose expression terms for a wide variety of >>>>>>>>> genes? >>>>>>>>> >>>>>>>>> >>>>>>>>> ------------------------------------------------------------------------------ >>>>>>>>> Download Intel® Parallel Studio Eval >>>>>>>>> Try the new software tools for yourself. Speed compiling, find >>>>>>>>> bugs >>>>>>>>> proactively, and fine-tune applications for parallel >>>>>>>>> performance. >>>>>>>>> See why Intel Parallel Studio got high marks during beta. >>>>>>>>> http://p.sf.net/sfu/intel-sw-dev >>>>>>>>> _______________________________________________ >>>>>>>>> Obo-human-phenotype mailing list >>>>>>>>> Obo...@li... >>>>>>>>> https://lists.sourceforge.net/lists/listinfo/obo-human- >>>>>>>>> phenotype >>>>>>>>> >>>>>>>> Dr. med. Sandra Dölken >>>>>>>> Charité Universitätsmedizin Berlin >>>>>>>> Campus Virchow Klinikum >>>>>>>> Institut für Medizinische Genetik >>>>>>>> Augustenburger Platz 1 >>>>>>>> 13353 Berlin >>>>>>>> Germany >>>>>>>> phone: +49(0)30 450 569 132 >>>>>>>> fax: +49(0)30 450 569 914 >>>>>>>> email: san...@ch... >>>>>>>> http://genetik.charite.de/institut/ >>>>>>>> >>>>>>>> >>>>>>>> ------------------------------------------------------------------------------ >>>>>>>> Download Intel® Parallel Studio Eval >>>>>>>> Try the new software tools for yourself. Speed compiling, find >>>>>>>> bugs >>>>>>>> proactively, and fine-tune applications for parallel >>>>>>>> performance. >>>>>>>> See why Intel Parallel Studio got high marks during beta. >>>>>>>> http://p.sf.net/sfu/intel-sw-dev >>>>>>>> _______________________________________________ >>>>>>>> Obo-human-phenotype mailing list >>>>>>>> Obo...@li... >>>>>>>> https://lists.sourceforge.net/lists/listinfo/obo-human-phenotype >>>>>>>> . >>>>>>>> >>>>>>> -- >>>>>>> Dr. med. Peter N. Robinson, MSc. >>>>>>> Institut für Medizinische Genetik >>>>>>> Charité - Universitätsmedizin Berlin >>>>>>> Humboldt-Universität >>>>>>> Augustenburger Platz 1 >>>>>>> 13353 Berlin >>>>>>> Germany >>>>>>> voice: 49-30-450566042 >>>>>>> fax: 49-30-450569915 >>>>>>> email: pet...@ch... >>>>>>> http://compbio.charite.de/ >>>>>>> http://www.human-phenotype-ontology.org >>>>>>> >>>>>>> ------------------------------------------------------------------------------ >>>>>>> Download Intel® Parallel Studio Eval >>>>>>> Try the new software tools for yourself. Speed compiling, find >>>>>>> bugs >>>>>>> proactively, and fine-tune applications for parallel performance. >>>>>>> See why Intel Parallel Studio got high marks during beta. >>>>>>> http://p.sf.net/sfu/intel-sw-dev >>>>>>> _______________________________________________ >>>>>>> Obo-human-phenotype mailing list >>>>>>> Obo...@li... >>>>>>> https://lists.sourceforge.net/lists/listinfo/obo-human-phenotype >>>>>> --------------------------------------------------- >>>>>> Dr. G.V.Gkoutos >>>>>> >>>>>> University of Cambridge >>>>>> Department of Genetics >>>>>> Downing Site, Downing Street >>>>>> Cambridge, CB2 3EH >>>>>> >>>>>> Tel: +44 [0] 1223 333963 >>>>>> >>>>>> email: gg...@ca... >>>>>> url: http://www.gen.cam.ac.uk >>>>>> >>>>>> ------------------------------------------------------ >>>>>> >>>>>> >>>>>> >>>>>> >>>>>> ------------------------------------------------------------------------------ >>>>>> Download Intel® Parallel Studio Eval >>>>>> Try the new software tools for yourself. Speed compiling, find >>>>>> bugs >>>>>> proactively, and fine-tune applications for parallel performance. >>>>>> See why Intel Parallel Studio got high marks during beta. >>>>>> http://p.sf.net/sfu/intel-sw-dev_______________________________________________ >>>>>> Obo-human-phenotype mailing list >>>>>> Obo...@li... >>>>>> https://lists.sourceforge.net/lists/listinfo/obo-human-phenotype >>>> --------------------------------------------------- >>>> Dr. G.V.Gkoutos >>>> >>>> University of Cambridge >>>> Department of Genetics >>>> Downing Site, Downing Street >>>> Cambridge, CB2 3EH >>>> >>>> Tel: +44 [0] 1223 333963 >>>> >>>> email: gg...@ca... >>>> url: http://www.gen.cam.ac.uk >>>> >>>> ------------------------------------------------------ >>>> >>>> >>>> >>>> >>>> >>>> ------------------------------------------------------------------------------ >>>> Download Intel® Parallel Studio Eval >>>> Try the new software tools for yourself. Speed compiling, find bugs >>>> proactively, and fine-tune applications for parallel performance. >>>> See why Intel Parallel Studio got high marks during beta. >>>> http://p.sf.net/sfu/intel-sw-dev >>>> _______________________________________________ >>>> Obo-human-phenotype mailing list >>>> Obo...@li... >>>> https://lists.sourceforge.net/lists/listinfo/obo-human-phenotype >>>> >>> >>> ------------------------------------------------------------------------------ >>> Download Intel® Parallel Studio Eval >>> Try the new software tools for yourself. Speed compiling, find bugs >>> proactively, and fine-tune applications for parallel performance. >>> See why Intel Parallel Studio got high marks during beta. >>> http://p.sf.net/sfu/intel-sw-dev >>> _______________________________________________ >>> Obo-human-phenotype mailing list >>> Obo...@li... >>> https://lists.sourceforge.net/lists/listinfo/obo-human-phenotype >>> . >>> >> >> -- >> Dr. med. Peter N. Robinson, MSc. >> Institut für Medizinische Genetik >> Charité - Universitätsmedizin Berlin >> Humboldt-Universität >> Augustenburger Platz 1 >> 13353 Berlin >> Germany >> voice: 49-30-450566042 >> fax: 49-30-450569915 >> email: pet...@ch... >> http://compbio.charite.de/ >> http://www.human-phenotype-ontology.org >> >> ------------------------------------------------------------------------------ >> Download Intel® Parallel Studio Eval >> Try the new software tools for yourself. Speed compiling, find bugs >> proactively, and fine-tune applications for parallel performance. >> See why Intel Parallel Studio got high marks during beta. >> http://p.sf.net/sfu/intel-sw-dev >> _______________________________________________ >> Obo-human-phenotype mailing list >> Obo...@li... >> https://lists.sourceforge.net/lists/listinfo/obo-human-phenotype > > . > -- Dr. med. Peter N. Robinson, MSc. Institut für Medizinische Genetik Charité - Universitätsmedizin Berlin Humboldt-Universität Augustenburger Platz 1 13353 Berlin Germany voice: 49-30-450566042 fax: 49-30-450569915 email: pet...@ch... http://compbio.charite.de/ http://www.human-phenotype-ontology.org |