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Phillippy, A.

Publications and source records attributed to Phillippy, A..

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MetaMaps - Strain-level metagenomic assignment and compositional estimation for long reads

Metagenomic sequence classification should be fast, accurate and information-rich. Emerging long-read sequencing technologies promise to improve the balance between these factors but most existing methods were designed for short reads. MetaMaps is a new method, specifically developed for long reads, that combines the accuracy of slower alignment-based methods with the scalability of faster k-mer-based methods. Using an approximate mapping algorithm, it is capable of mapping a long-read metagenome to a comprehensive RefSeq database with >12,000 genomes in <30 GB or RAM on a laptop computer. Integrating these mappings with a probabilistic scoring scheme and EM-based estimation of sample composition, MetaMaps achieves >95% accuracy for species-level read assignment and r2 > 0.98 for the estimation of sample composition on both simulated and real data. Uniquely, MetaMaps outputs mapping locations and qualities for all classified reads, enabling functional studies (e.g. gene presence/absence) and the detection of novel species not present in the current database.\n\nAvailability and ImplementationMetaMaps is implemented in C++/Perl and freely available from https://github.com/DiltheyLab/MetaMaps (GPL v3).

bioinformatics

Complete assembly of parental haplotypes with trio binning

Reference genome projects have historically selected inbred individuals to minimize heterozygosity and simplify assembly. We challenge this dogma and present a new approach designed specifically for heterozygous genomes. \"Trio binning\" uses short reads from two parental genomes to partition long reads from an offspring into haplotype-specific sets prior to assembly. Each haplotype is then assembled independently, resulting in a complete diploid reconstruction. On a benchmark human trio, this method achieved high accuracy and recovered complex structural variants missed by alternative approaches. To demonstrate its effectiveness on a heterozygous genome, we sequenced an F1 cross between cattle subspecies Bos taurus taurus and Bos taurus indicus, and completely assembled both parental haplotypes with NG50 haplotig sizes >20 Mbp and 99.998% accuracy, surpassing the quality of current cattle reference genomes. We propose trio binning as a new best practice for diploid genome assembly that will enable new studies of haplotype variation and inheritance.

genomics