A method of detecting cells of a cancer type in a subject, the method comprising: (i) capturing cell-free DNA (cfDNA) fragments from the subject or amplification products thereof with a composition comprising a plurality of different bait oligonucleotides, wherein: (a) each bait oligonucleotide in the plurality of different bait oligonucleotides has a length of at least 45 nucleotides, optionally 45 to 300 nucleotides; (b) the bait oligonucleotides collectively hybridize to at least 100 target genomic regions that are differentially methylated in a first cancer type of at least 10 cancer types, relative to a different cancer type of the at least 10 cancer types or relative to non-cancer; (ii) sequencing the captured cfDNA fragments or amplification products thereof to produce sequencing reads, wherein the cfDNA is converted prior to sequencing by treating the cfDNA to convert unmethylated cytosines to uracils, and (iii) for each of the at least 10 cancer types, applying a trained classifier to the sequencing reads, wherein the classifier (a) is constrained to the at least 100 target genomic regions of the bait oligonucleotides for the first cancer type, and (b) assigns a score for each of the at least 10 cancer types; wherein the trained classifier is a classifier trained using converted DNA sequences, wherein converted DNA relates to DNA that has been treated to convert unmethylated cytosines to uracils, and (iv) detecting the cells of the cancer type in the subject as the cancer type assigned the highest score; wherein the at least 10 cancer types are selected from anorectal cancer, bladder cancer, urothelial cancer, breast cancer, cervical cancer, colorectal cancer, head & neck cancer, liver cancer, bile duct cancer, lung cancer, ovarian cancer, pancreatic cancer, gallbladder cancer, prostate cancer, renal cancer, sarcoma, thyroid cancer, upper GI cancer, and uterine cancer. (i) capturing cell-free DNA (cfDNA) fragments from the subject or amplification products thereof with a composition comprising a plurality of different bait oligonucleotides, wherein: (a) each bait oligonucleotide in the plurality of different bait oligonucleotides has a length of at least 45 nucleotides, optionally 45 to 300 nucleotides; (b) the bait oligonucleotides collectively hybridize to at least 100 target genomic regions that are differentially methylated in a first cancer type of at least 10 cancer types, relative to a different cancer type of the at least 10 cancer types or relative to non-cancer; (a) each bait oligonucleotide in the plurality of different bait oligonucleotides has a length of at least 45 nucleotides, optionally 45 to 300 nucleotides; (b) the bait oligonucleotides collectively hybridize to at least 100 target genomic regions that are differentially methylated in a first cancer type of at least 10 cancer types, relative to a different cancer type of the at least 10 cancer types or relative to non-cancer; (ii) sequencing the captured cfDNA fragments or amplification products thereof to produce sequencing reads, wherein the cfDNA is converted prior to sequencing by treating the cfDNA to convert unmethylated cytosines to uracils, and (iii) for each of the at least 10 cancer types, applying a trained classifier to the sequencing reads, wherein the classifier (a) is constrained to the at least 100 target genomic regions of the bait oligonucleotides for the first cancer type, and (b) assigns a score for each of the at least 10 cancer types; wherein the trained classifier is a classifier trained using converted DNA sequences, wherein converted DNA relates to DNA that has been treated to convert unmethylated cytosines to uracils, and (iv) detecting the cells of the cancer type in the subject as the cancer type assigned the highest score;