TABLE 3.

Clinical data sets analyzed in this study^a

Data source or BioProject accession no. (study authors [reference{s}])	Disease type(s)	Sample type(s)	Data set type(s)	Clinical data provided by the study to compare to MDRE service results	Pipeline(s) compared to UltraSEQ
https://veb.lumc.nl/CliniMG (de Vries et al. [24])	Encephalitis and respiratory	CSF, brain, NP, BAL fluid, nasal wash, plasma	DNA and RNA reads	qPCR-positive patient samples (n = 13)	9 pipelines from reference 24
PRJNA516289 (Miller et al. [10])b	Encephalitis/meningitis	CSF	Illumina RNA and DNA reads	Original clinical tests (n = 216 tests) from 95 patient samplesc	SURPI
PRJNA516582 (Saha et al. [12])	Encephalitis/meningitis	CSF	Illumina RNA reads	Clinical culture-, antigen-, or PCR-positive specimens (n = 36) from patients with neurologic infections based on negative specimens (n = 30) from patients with an alternate diagnosis; CHIKV PCR-positive specimens (n = 17); confirmed cases from an idiopathic set (n = 11)c	IDseq with logistic regression model
CSF_metagenomics from idseq.net (Hasan et al. [13])	Encephalitis/meningitis	CSF	Illumina DNA reads	Culture- and/or PCR-positive residual specimens (n = 74) from patients with suspected CNS infectionsd	IDseq
PRJEB7888 (Fischer et al. [15])	Respiratory	BAL fluid, sputum, nasal swab	Illumina RNA reads	Influenza PCR-positive respiratory specimens (n = 24) from patients with seasonal influenza infection and samples (n = 5) from patients with pneumonia that tested negative for influenza	Fischer et al.’s pipeline and Explify
PRJNA554856 (Watts et al. [16])	Respiratory	Endotracheal exudate	IonTorrent DNA reads	Culture-positive patient samples (n = 2)	Centrifuge and resistance gene identifier
PRJNA554461 (Yang et al. [18])	Respiratory	Endotracheal exudate	MinION DNA reads	Samples from patients (n = 14) with VAP, including culture positive (n = 9), culture negative (n = 5), and controls (n = 8) (patients without pneumonia)	WIMP
PRJEB13360 (Flygare et al. [19] and Graf et al. [20])	Respiratory	Pediatric NP/OP	Illumina RNA reads	PCR-positive samples (n = 24); no negative controls	Explify
PRJNA634356 (Babiker et al. [22])	Respiratory	NP	Illumina RNA reads	RT-PCR-negative (n = 30) and SARS-CoV-2 RT-PCR- and other PCR-positive patients with coinfections (n = 45)	Explify and KrakenUniq
Battelle (this study)	Respiratory	Saliva	Illumina RNA reads	SARS-CoV-2 RT-PCR-positive patients (n = 8)	NA

^aCSF, cerebral spinal fluid; BAL, bronchial lavage; VAP, ventilator-associated pneumonia; NP, nasopharyngeal; OP, oropharyngeal; NA, not applicable; CHIKV, chikungunya virus; CNS, central nervous system.

^bNote that for this case study, 89 samples were run for comparison to the data in Fig. 1B in reference 10. RNAseq data sets were run for RNA viruses, and DNAseq data sets were run for the rest. The 20 “challenge” samples (see Table S3 in the supplemental material in reference 10) were not included since the sample identifiers could not be matched to the raw data files. See “All Organisms” in Table S2 in the supplemental material in reference 10 (“MNA” identifications match up to the raw data sample identifications).

^cNote that an additional 24 idiopathic meningitis cases (n = 24) were reported by those authors (12), but only those with confirmed tests were included in this study.

^dNote that reads could be downloaded only with host reads subtracted in FASTQ format (raw files were not available). Furthermore, only 20 samples were available. Since most of these are true negatives, 5 samples with confirmed truth tests were selected for a proof-of-concept comparison to IDseq results.