We present a new method for determining the consensus sequence in DNA fragment assemblies. The new method, Trace-Evidence, directly incorporates aligned ABI trace information into consensus calculations via our previously described representation, Trace-Data Classifications. The new method extracts and sums evidence indicated by the representation to determine consensus calls. Using the Trace-Evidence method results in automatically produced consensus sequences that are more accurate and less ambiguous than those produced with standard majorityvoting methods. Additionally, these improvements are achieved with less coverage than required by the standard methods - using Trace-Evidence and a coverage of only three, error rates are as low as those with a coverage of over ten sequences.
Note: The title of this post is circular. But I use/abuse it because of the post linked below. I noticed on the Hacker News front page (and via multiple reshares on twitter), a discussion on why logistic regression uses a sigmoid. The article linked in the story talks about the log-odds ratio, and how it leads to the sigmoid (and gives a good intuitive plug on it). However, I think that the more important question is – Why do you care about log-odds?
Metagenomics characterizes the taxonomic diversity of microbial communities by sequencing DNA directly from an environmental sample. One of the main challenges in metagenomics data analysis is the binning step, where each sequenced read is assigned to a taxonomic clade. Due to the large volume of metagenomics datasets, binning methods need fast and accurate algorithms that can operate with reasonable computing requirements. While standard alignment-based methods provide state-of-the-art performance, compositional approaches that assign a taxonomic class to a DNA read based on the k-mers it contains have the potential to provide faster solutions. In this work, we investigate the potential of modern, large-scale machine learning implementations for taxonomic affectation of next-generation sequencing reads based on their k-mers profile. We show that machine learning-based compositional approaches benefit from increasing the number of fragments sampled from reference genome to tune their parameters, up to a coverage of about 10, and from increasing the k-mer size to about 12. Tuning these models involves training a machine learning model on about 10 8 samples in 10 7 dimensions, which is out of reach of standard soft-wares but can be done efficiently with modern implementations for large-scale machine learning. The resulting models are competitive in terms of accuracy with well-established alignment tools for problems involving a small to moderate number of candidate species, and for reasonable amounts of sequencing errors. We show, however, that compositional approaches are still limited in their ability to deal with problems involving a greater number of species, and more sensitive to sequencing errors. We finally confirm that compositional approach achieve faster prediction times, with a gain of 3 to 15 times with respect to the BWA-MEM short read mapper, depending on the number of candidate species and the level of sequencing noise.
We introduce the notion of pointwise coverage to measure the explainability properties of machine learning classifiers. An explanation for a prediction is a definably simple region of the feature space sharing the same label as the prediction, and the coverage of an explanation measures its size or generalizability. With this notion of explanation, we investigate whether or not there is a natural characterization of the most explainable classifier. According with our intuitions, we prove that the binary linear classifier is uniquely the most explainable classifier up to negligible sets.