Table 1.

An non-exhaustive list of the mechanistic model-based vs. ML tools for microbial genome analysis.

Category	Tools
	Mechanistic model-based	Machine learning
DE NOVO GENOME ASSEMBLY
	Velvet (Zerbino and Birney, 2008), IDBA-UD (Peng et al., 2012), RAY (Boisvert et al., 2010), SPAdes (Bankevich et al., 2012), SKESA (Souvorov et al., 2018) Minimap/miniasm (Li, 2016), Canu (Koren et al., 2017), REAGO** (Yuan et al., 2015)	PERGA (Zhu et al., 2014), Minimus/AMOS (Palmer et al., 2010), MetaVelvet-SL* (Cheng, 2015)
GENOME CHARACTERIZATION
1. Bacterial strain identification	BLASTN (McGinnis and Madden, 2004), JSpeciesWS (Richter et al., 2016), ANItools (Han et al., 2016), OrthoANI (Lee et al., 2016), KmerFinder (Hasman et al., 2014), StrainSeeker (Roosaare et al., 2017), MESH (Ondov et al., 2016), Kraken* (Wood and Salzberg, 2014), MetaPhlAn* (Segata et al., 2012), QIIME2** (Caporaso et al., 2010), MOTHUR** (Schloss et al., 2009), MG-RAST** (Meyer et al., 2008)	PaPrBaG (Deneke et al., 2017), NBC (Rosen et al., 2008), TACOA (Diaz et al., 2009), PhyloPythiaS+* (McHardy et al., 2007; Gregor et al., 2016), BLCA** (Gao et al., 2017), 16S Classifier** (Chaudhary et al., 2015)
2. Bacterial genome annotation	PROKKA (Seemann, 2014), RAST/myRAST (Overbeek et al., 2014), MetaGeneAnnotator* (Noguchi et al., 2008), MetaGene* (Noguchi et al., 2006), Tax4Fun** (Aßhauer et al., 2015)	Woods (Sharma et al., 2015), Orphelia* (Hoff et al., 2009), MGC* (El Allali and Rose, 2013), MetaGUN* (Liu et al., 2013), Meta-MFDL* (Chen et al., 2016)
3. Virulence gene detection	VirulenceFinder (Joensen et al., 2014), PathogenFinder (Cosentino et al., 2013)	BacFier (Iraola et al., 2012), PaPrBaG (Deneke et al., 2017)
4. Antimicrobial resistance gene detection	ResFinder (Zankari et al., 2012), RGI/CARD (Jia et al., 2017), AMRFinder (Feldgarden et al., 2019)	DeepARG (Arango-Argoty et al., 2018), PATRIC (Antonopoulos et al., 2017)
COMPARATIVE GENOMICS
1. Reference-based SNP methods	CSI Phylogeny (Kaas et al., 2014), Lyve-SET (Katz et al., 2017), CFSAN SNP Pipeline (Davis et al., 2015), SPANDx (Sarovich and Price, 2014), SNVPhyl (Petkau et al., 2017)
2. Non-reference-based SNP analysis	KSNP (Gardner et al., 2015)
3. Pangenome-based analysis	Roary (Page et al., 2015), PanWeb (Pantoja et al., 2017), Pan-Seq (Laing et al., 2010)
4. Core genome/whole-genome multi-locus sequence typing (MLST)	EnteroBase (Alikhan et al., 2018), BIGSdb (Jolley and Maiden, 2010), chewBBACA (Silva et al., 2018)	BAPS/hierBAPS (Cheng et al., 2011, 2013)
PHYLOGENOMICS
	RAxML (Stamatakis et al., 2005), FastTree (Price et al., 2009), CSI Phylogeny (Kanamori et al., 2015), Lyve-SET (Katz et al., 2017), PHYLIP (Shimada and Nishida, 2017), BEAST (Drummond and Rambaut, 2007)

^*The tool is dedicated to shotgun metagenomics;

^**the tool dedicated to 16S metataxonomics.