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We present TIPP3 and TIPP3-fast, new tools for abundance profiling in metagenomic datasets. Like its predecessor, TIPP2, the TIPP3 pipeline uses a maximum likelihood approach to place reads into labeled taxonomies using marker genes, but it achieves superior accuracy to TIPP2 by enabling the use of much larger taxonomies through improved algorithmic techniques. We show that TIPP3 is generally more accurate than leading methods for abundance profiling in two important contexts: when reads come from genomes not already in a public database (i.e., novel genomes) and when reads contain sequencing errors. We also show that TIPP3-fast has slightly lower accuracy than TIPP3, but is also generally more accurate than other leading methods and uses a small fraction of TIPP3’s runtime. Additionally, we highlight the potential benefits of restricting abundance profiling methods to those reads that map to marker genes (i.e., using a filtered marker-gene based analysis), which we show typically improves accuracy. TIPP3 is freely available athttps://github.com/c5shen/TIPP3.