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FragAssembly - Fragment Assembly 1 Introduction Fragments...

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02/10/12 1 Fragment Assembly
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02/10/12 2 Introduction Fragments are typically of 200-700 bp long “Target” string is about 30k – 100k bp long Problem: given a set of fragments reconstruct the target
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02/10/12 3 Introduction Multiple-alignment of the fragments ignoring spaces at the end The alignment is called “layout” The output is called the “consensus sequence” An optimization problem
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02/10/12 4 Complications Base-call errors: Substitution errors [p 107] Insertion errors (possibly from the host sequence) [p 108, fig 4.3] Deletion error [fig 4.4] Majority voting solves them (or some form of optimization)
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02/10/12 5 Complications Chimeras : To non-contiguous fragments get joined as a single fragment [p 109, fig 4.5] Needs to be weeded out as a preprocessing step Similar to chimeras, contaminant fragments (possibly from host) needs to be filtered out as well
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02/10/12 6 Complications Unknown orientation: Fragments may come from either strand Even from the opposite strand, its reverse-complement must be in the target string Consequence: try both forward and rev- complement of each fragment (2^n trial in worst, for n fragments) [p 109, fig 4.6]
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02/10/12 7 Complications Repeats : Regions (super-string of some fragments) may repeat in a target Consequent problem: where do the fragments really come from, on approximate alignment? [p 110, fig 4.7] Problem 2: where should the inter-repeat fragments go? [p111, fig 4.8, fig 4.9] Inverted repeats: repeat of the reverse complement [fig 4.10]
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02/10/12 8 Complications Insufficient coverage: Chance of coverage increases with redundancy (a heuristic: cover 8 times the target length) Chance of covering a gap reduces when it remains uncovered even after multiple fragments are aligned): random sampling is not good solution here
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02/10/12 9 Complications Insufficient coverage: What you get with insufficient coverage is multiple “contigs,” not one contig
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