Analysis of nucleic acids associated with extracellular vesicles in pregnant females

A method comprising:

• receiving a blood sample of a female having a pregnancy with a fetus, the blood sample including extracellular particles and particle-free nucleic acids, wherein the extracellular particles include cell-free nucleic acids inside of membranes;
• performing a physical separation technique that preferentially selects at least a portion of the extracellular particles, thereby obtaining a particle-enriched sample;
• treating the particle-enriched sample using a treatment technique that removes excess particle-free nucleic acids, thereby obtaining a treated particle-enriched sample, the treatment technique including washing the particle-enriched sample with an ionic solution and applying a nuclease to the particle-enriched sample, wherein the treatment technique increases a fractional concentration of fetal nucleic acids in the treated particle-enriched sample relative to the particle-enriched sample;
• exposing cell-free nucleic acid molecules from the extracellular particles by disrupting membranes of the extracellular particles;
• assaying the cell-free nucleic acid molecules to obtain sequence reads;
• and
• analyzing the sequence reads to determine a genomic characteristic of the fetus or of the pregnancy of the female.

A method comprising:

• receiving a blood sample of a female having a pregnancy with a fetus, the blood sample including extracellular particles and particle-free nucleic acids, wherein the extracellular particles include cell-free nucleic acids inside of membranes;
• performing one or more purification steps that enrich for the extracellular particles, thereby producing an enriched sample;
• exposing cell-free nucleic acid molecules from the extracellular particles by disrupting membranes of the extracellular particles;
• sequencing, using a sequencing technique, the cell-free nucleic acid molecules to obtain sequence reads, wherein at least a portion of the sequence reads are more than 600 bp;
• and
• analyzing the sequence reads to determine a genomic characteristic of the fetus or of the pregnancy of the female.