Limitations
DNA sequencing theories often invoke the assumption that certain random variables in a model are independently and identically distributed. For example, in Lander–Waterman Theory, a sequenced fragment is presumed to have the same probability of covering each region of a genome and all fragments are assumed to be independent of one another. In actuality, sequencing projects are subject to various types of bias, including differences of how well regions can be cloned, sequencing anomalies, biases in the target sequence (which is not random), and software-dependent errors and biases. In general, theory will agree well with observation up to the point that enough data have been generated to expose latent biases. The kinds of biases related to the underlying target sequence are particularly difficult to model, since the sequence itself may not be known a priori. This presents a type of "chicken and egg" closure problem.
Read more about this topic: DNA Sequencing Theory
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