Search for: All records

Metagenomes encode an enormous diversity of proteins, reflecting a multiplicity of functions and activities. Exploration of this vast sequence space has been limited to a comparative analysis against reference microbial genomes and protein families derived from those genomes. Here, to examine the scale of yet untapped functional diversity beyond what is currently possible through the lens of reference genomes, we develop a computational approach to generate reference-free protein families from the sequence space in metagenomes. We analyze 26,931 metagenomes and identify 1.17 billion protein sequences longer than 35 amino acids with no similarity to any sequences from 102,491 reference genomes or the Pfam database. Using massively parallel graph-based clustering, we group these proteins into 106,198 novel sequence clusters with more than 100 members, doubling the number of protein families obtained from the reference genomes clustered using the same approach. We annotate these families on the basis of their taxonomic, habitat, geographical, and gene neighborhood distributions and, where sufficient sequence diversity is available, predict protein three-dimensional models, revealing novel structures. Overall, our results uncover an enormously diverse functional space, highlighting the importance of further exploring the microbial functional dark matter. 

In 2013, we released a position paper to launch a community effort to define a common set of building blocks for constructing graph algorithms in the language of linear algebra. This led to the GraphBLAS. We released a specification for the C programming language binding to the GraphBLAS in 2017. Since that release, multiple libraries that conform to the GraphBLAS C specification have been produced. In this position paper, we launch the next phase of this ongoing community effort: a project to assemble a set of high level graph algorithms built on top of the GraphBLAS. While many of these algorithms are well-known with high quality implementations available, they have not been assembled in one place and integrated with the GraphBLAS. We call this project the LAGraph graph algorithms project and with this position paper, we put out a call for collaborators to join us. While the initial goal is to just assemble these algorithms into a single framework, the long term goal is a library of production-worthy code, with the LAGraph library serving as an open source repository of verified graph algorithms that use the GraphBLAS. 

Abstract Evaluating metagenomic software is key for optimizing metagenome interpretation and focus of the Initiative for the Critical Assessment of Metagenome Interpretation (CAMI). The CAMI II challenge engaged the community to assess methods on realistic and complex datasets with long- and short-read sequences, created computationally from around 1,700 new and known genomes, as well as 600 new plasmids and viruses. Here we analyze 5,002 results by 76 program versions. Substantial improvements were seen in assembly, some due to long-read data. Related strains still were challenging for assembly and genome recovery through binning, as was assembly quality for the latter. Profilers markedly matured, with taxon profilers and binners excelling at higher bacterial ranks, but underperforming for viruses and Archaea. Clinical pathogen detection results revealed a need to improve reproducibility. Runtime and memory usage analyses identified efficient programs, including top performers with other metrics. The results identify challenges and guide researchers in selecting methods for analyses.