Strain profiling with StrainPhlAn Curtis Huttenhower Galeb Abu-Ali Eric Franzosa 08-12-16 Harvard T.H. Chan School of Public Health Department of Biostatistics

Efficient assembly-free meta’omics by leveraging isolates II III IV V I II III IV V II III II I IV I I II III II V IV V V Species pan-genomes 7,677 containing 18.6 million gene clusters Core genes Marker genes NCBI isolate genomes Archaea 300 Bacteria 12,926 Viruses 3,565 Eukaryota 112 Open reading frames 49.0 million total genes Nicola Segata RepoPhlAn ChocoPhlAn http://www.metaref.org

PanPhlAn: the approach http://bitbucket.org/CibioCM/panphlan mapping Read Metagenomic sample Gene coverage Microbial pangenomes Cluster to Gene families Pan-gene family coverage Abundance-sorted pan-gene families Coverage Multi-copy genes Plateau of genes from one metagenome’s strain Absent genes

PanPhlAn for “meta-epidemiology” http://bitbucket.org/CibioCM/panphlan Metagenomes from [Loman et al., 2013]

Strain-level tracking with other species Prevotella copri

Synthetic and semi-synthetic validation Coverage Coverage Coverage Coverage Coverage

StrainPhlAn: metagenomic strain identification and tracking

A tool for strain level population genomics China Denmark Estonia Finland Peru’ Hungary Italy Norway France Spain Sweden USA Germany P. copri as an example species Alignment length: 66k nt Median SNPs: 830 [3.6%] # pos. samples: 123

A tool for strain level population genomics Alignment length: 62k nt Median SNPs: 830 [1.3%] # pos. samples: 123

Strains in the HMP1-II

Most bugs are dominated by one stable strain

Most bugs are dominated by one stable strain

There’s a lot of strain-level variation left to discover

There’s a lot of strain-level variation left to discover

Thanks! http://huttenhower.sph.harvard.edu Human Microbiome Project 2 Lita Procter Jon Braun Dermot McGovern Subra Kugathasan Ted Denson Janet Jansson Bruce Birren Chad Nusbaum Clary Clish Joe Petrosino Thad Stappenbeck Alex Kostic Ayshwarya Subramanian Xochitl Morgan Casey DuLong Daniela Boernigen Lauren McIver Ramnik Xavier Human Microbiome Project Jane Peterson Sarah Highlander Barbara Methe Karen Nelson George Weinstock Owen White George Weingart Emma Schwager Eric Franzosa Boyu Ren Tiffany Hsu Ali Rahnavard Hera Vlamakis Finally, thanks again to the ISMB organizers and ISCB for putting together a fantastic conference as always, to our funders, the rest of my lab back in Boston, our collaborators, and everyone in the audience today – many thanks again. Levi Waldron Joseph Moon Jim Kaminski Tommi Vatanen Koji Yasuda Siyuan Ma Galeb Abu-Ali Dirk Gevers Nicola Segata Clary Clish Justin Scott Wendy Garrett Bahar Sayoldin Randall Schwager Melanie Schirmer Himel Mallick Moran Yassour Alexandra Sirota-Madi