hms_9675

hms_9675 - Harvard-MIT Division of Health Sciences and...

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Limitations of massively parallel technologies Zoltan Szallasi, MD Children’s Hospital Informatics Program www.chip.org Harvard-MIT Division of Health Sciences and Technology HST.512: Genomic Medicine Prof. Zoltan Szallasi
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New technology All problems will be solved within a couple of years Realistic Expectations (limitations)
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Limitations: (you want to make predictions) Accuracy – noise Sensitivity - completeness Inherent limitations – (think about unpredictability > chaos)
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NOISE: - what is noise ? (and what is signal ?) - noise as an inherent feature of complex systems - noise in continuous and discrete measurements - noise as the limitation of the technology - what can be done about noise ? Statistics Normalization as a way to deal with systematic errors
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c : an unwanted signal or a disturbance (as static or a variation of voltage) in an electronic device or instrument (as radio or television); broadly : a disturbance interfering with the operation of a usually mechanical device or system d : electromagnetic radiation (as light or radio waves) that is composed of several frequencies and that involves random changes in frequency or amplitude e : irrelevant or meaningless data or output occurring along with desired information
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Noise may turn out to be an important signal !!!! - Penzias and Wilson >>> cosmic background radiation - discovery of the chemotherapeutic agent cis-platinum
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What we perceive as noise/error might be a key component of biological processes: 1) Mutations in evolution 2) “Junk” DNA 3) Asymmetric cell division may contribute to differentiation 4) Stochastic fluctuations may be important for the stability of complex physicochemical systems
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Genetic networks are stochastic systems: 1) A couple of hundred copies of a given transcription factor/nucleus 2) Intracellular environment is the not a free solution 3) Reaction kinetics is often slow etc. A B C D E F A B C D E F A B C D E F A B C D E F
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Please see Science. 2002 Aug 16; 297(5584):1183-6. Comment in: Science. 2002 Aug 16; 297(5584):1129-31. Stochastic gene expression in a single cell. Elowitz MB, Levine AJ, Siggia ED, Swain PS.
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- measuring population averaged data. That is true even if single cells are quantified due to stochasticity > two cells can get from a given state to another one via different paths
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Noise in measurements There is no measurement without noise - (it is the accuracy/sensitivity of your measurement that is low ) For continuous variables it is expected to obtain data with a certain “spread”
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- 0.5, -0.3, 0.2, 1.4, -1.5…. .etc what is the true value of the observed variable ? - Did the variable change due to a given treatment? Etc.
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hms_9675 - Harvard-MIT Division of Health Sciences and...

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