Methods for selective cell-free nucleic acid analysis

A method for processing a plurality of nucleic acid molecules derived from a cell-free biological sample, comprising (a) determining a methylation state fora nucleic acid molecule of said plurality of nucleic acid molecules;

• (b) determining a size for said nucleic acid molecule of said plurality of nucleic acid molecules;
• and (c) processing (i) said methylation state for said nucleic acid molecule of said plurality of nucleic acid molecules against a first database, and (ii) said size for said nucleic acid molecule of said plurality of nucleic acid molecules against a second database, to identify an association of said methylation state and of said size with at least a disease.

(canceled)

The method of claim to 37, wherein determining said methylation state comprises (a) bringing said plurality of nucleic acid molecules in contact with a plurality of binding agents, to provide a first subset of said plurality of nucleic acid molecules coupled to said plurality of binding agents and a second subset of said plurality of nucleic acid molecules;

• (b) separating said first subset of said plurality of nucleic acid molecules coupled to said plurality of binding agents from said second subset of said plurality of nucleic acid molecules;
• (c) subsequent to (b), circularizing a nucleic acid molecule derived from said first subset of said plurality of nucleic acid molecules to obtain a circularized nucleic acid molecule;
• and (d) identifying said circularized nucleic acid molecule or derivative thereof.

44 The method of claim 43, wherein said polypeptide comprises streptavidin.

-50. (canceled)

-55 (canceled)

(canceled)

58 The method of claim 37, further comprising processing said methylation state and against a plurality of reference methylation states and processing said size against a plurality of reference sizes to identify said methylation state as corresponding to at least a subset of said plurality of reference methylation states and said size as corresponding to at least a subset of said reference sizes, thereby determining that a subject has or is at risk of having a disease.

The method of claim 58, wherein said disease is cancer selected from the group consisting of colon cancer, non-small cell lung cancer, small cell lung cancer, breast cancer, hepatocellular carcinoma, liver cancer, skin cancer, malignant melanoma endometrial cancer, esophageal cancer, gastric cancer, ovarian cancer, pancreatic cancer, brain cancer, leukemia, lymphoma, and myeloma.

(canceled)

The method of claim 58, further comprising using said methylation state and said size identified to output an electronic report indicating that said subject has or is at risk of having a disease.

The method of claim 58, further comprising using said methylation state and said size identified to provide a therapeutic intervention to said subject for a disease, to treat said subject for said disease, or to monitor said subject for a progression or regression of said disease.

(canceled)

(canceled)