To benchmark our software, and ensure compatibility with existing approaches, six datasets were selected, and one raw file was downloaded from each of their respective GlycoPost accessions (Table ). To demonstrate broad applicability across multi-glycomics , these datasets cover a range of glycan types: N-glycans (NG), O-glycans (OG) and glycans released from glycosphingolipids (GSL). For suitability of different polarities and derivatisation states, we also included permethylated and native glycans acquired in positive and negative modes. The vendor-neutrality of our approach was also assessed with dataset generated on Bruker and Thermo Fisher Scientific instruments. GlyCombo was developed with three qualities in mind: broad accessibility, rapid output, and completeness of glycan detection. Benchmarking was performed by searching the same neutral mass list generated by GlyCombo between both GlycoMod and GlyCombo, using the same monosaccharide ranges, and search time was recorded in triplicate. As shown in Fig 3A , all datasets were compatible with our software and it generally performed faster than GlycoMod, with up to 3x faster search times. Despite this, dataset 3 was almost 2x slower with our software, causing these search speed discrepancies to be investigated. Unlike GlyCombo, GlycoMod (and other search tools such as GlycReSoft and GlycoNote ) utilise matching rules based on literature review and assumed biosynthetic pathways to limit the combinatorial burden. This is demonstrated by the GlycoMod N-glycan search function whereas the O-glycan search function does not have such rules beyond a mass limit of 5 kDa . A comparison of the number of glycan compositions identified based on the glycan masses observed in each dataset (Fig ) confirmed that the N-glycan search function yielded fewer matches, and when assessed with the O-glycan function, similar combinations were identified at longer search times (e.g. dataset 3 processing time increased from 180 to 550 seconds, 50% slower than GlyCombo). As multiple monosaccharide combinations can be matched to a single scan, a ratio greater than 1 is possible.