System for determining a health status of a tissue of interest

Abstract

The invention generally relates to methods for assessing the health of a tissue by characterizing circulating nucleic acids in a biological sample. According to certain embodiments, methods for assessing the health of a tissue include the steps of detecting a sample level of RNA in a biological sample, comparing the sample level of RNA to a reference level of RNA specific to the tissue, determining whether a difference exists between the sample level and the reference level, and characterizing the tissue as abnormal if a difference is detected.

What is claimed is: 
     
         1 . A method for determining that a pregnant subject or a fetus of said pregnant subject is at an elevated risk of a pregnancy-related health condition, comprising:
 (a) obtaining a biological sample from said pregnant subject;   (b) sequencing nucleic acid molecules derived from said biological sample to identify a set of ribonucleic acid (RNA) transcripts in said biological sample; and   (c) analyzing said set of RNA transcripts identified in (b) to determine that said pregnant subject or said fetus of said pregnant subject is at said elevated risk of said pregnancy-related health condition.   
     
     
         2 . The method of  claim 1 , wherein said biological sample is selected from the group consisting of a blood sample, serum sample, plasma sample, saliva sample, stool sample, sputum sample, urine sample, semen sample, transvaginal fluid sample, breast milk sample, breast fluid sample, breast nipple aspirate sample, cerebrospinal fluid sample, sweat sample, a cell biopsy sample, and a tissue biopsy sample. 
     
     
         3 . The method of  claim 1 , wherein said biological sample is a blood sample or a plasma sample. 
     
     
         4 . The method of  claim 1 , wherein sequencing said nucleic acid molecules comprises reverse transcribing RNA molecules derived from said biological sample to produce complementary deoxyribonucleic acid (cDNA) molecules, and sequencing said cDNA molecules or derivatives thereof to identify said set of RNA transcripts. 
     
     
         5 . The method of  claim 4 , further comprising amplifying said cDNA molecules to produce amplified products, and sequencing said amplified products or derivatives thereof to identify said set of RNA transcripts. 
     
     
         6 . The method of  claim 1 , wherein said pregnancy-related health condition comprises pre-term birth. 
     
     
         7 . The method of  claim 6 , wherein said pre-term birth is indicated by pre-eclampsia. 
     
     
         8 . The method of  claim 1 , wherein said pregnancy-related health condition comprises pre-eclampsia. 
     
     
         9 . The method of  claim 1 , wherein said pregnancy-related health condition comprises one or more anomalies in pregnancy. 
     
     
         10 . The method of  claim 1 , wherein said pregnancy-related health condition comprises one or more anomalies in fetal development. 
     
     
         11 . The method of  claim 1 , wherein said set of RNA transcripts comprises one or more tissue-specific differentially expressed transcripts. 
     
     
         12 . The method of  claim 11 , wherein said one or more tissue-specific differentially expressed transcripts comprise one or more maternal-specific transcripts. 
     
     
         13 . The method of  claim 11 , wherein said one or more tissue-specific differentially expressed transcripts comprise one or more placental-specific transcripts. 
     
     
         14 . The method of  claim 11 , wherein said one or more tissue-specific differentially expressed transcripts comprise one or more fetal-specific transcripts. 
     
     
         15 . The method of  claim 14 , wherein said one or more fetal-specific transcripts comprise one or more transcripts corresponding to a fetal tissue type selected from the group consisting of: brain, liver, thymus, and lung. 
     
     
         16 . The method of  claim 1 , further comprising identifying a clinical intervention for said pregnant subject or said fetus of said pregnant subject based at least in part on said elevated risk of said pregnancy-related health condition determined in (c). 
     
     
         17 . The method of  claim 16 , wherein said clinical intervention comprises a drug treatment. 
     
     
         18 . The method of  claim 1 , wherein said set of RNA transcripts comprises one or more pregnancy-associated differentially expressed transcripts. 
     
     
         19 . The method of  claim 1 , wherein said pregnant subject is in a first trimester of pregnancy. 
     
     
         20 . The method of  claim 1 , wherein said pregnant subject is in a second trimester of pregnancy. 
     
     
         21 . The method of  claim 1 , wherein said pregnant subject is in a third trimester of pregnancy. 
     
     
         22 . The method of  claim 1 , wherein analyzing said set of RNA transcripts comprises processing said set of RNA transcripts with a reference. 
     
     
         23 . The method of  claim 22 , wherein said reference corresponds to a set of RNA transcripts from one or more non-pregnant subjects. 
     
     
         24 . The method of  claim 22 , wherein said reference corresponds to a set of RNA transcripts from one or more pregnant subjects. 
     
     
         25 . The method of  claim 22 , wherein analyzing said set of RNA transcripts comprises identifying a difference between said set of RNA transcripts and said reference. 
     
     
         26 . The method of  claim 25 , further comprising determining a level of fold change in quantitative polymerase chain reaction (qPCR) measurements based at least in part on data corresponding to said set of RNA transcripts and said reference to identify said difference. 
     
     
         27 . The method of  claim 25 , further comprising performing principle component analysis on data corresponding to said set of RNA transcripts and said reference to identify said difference. 
     
     
         28 . The method of  claim 25 , further comprising using said difference to determine said elevated risk of said pregnancy-related health condition. 
     
     
         29 . The method of  claim 1 , further comprising analyzing sets of RNA transcripts in biological samples obtained at two or more different time points, and comparing the analyzed sets of RNA transcripts to each other to determine that said pregnant subject or said fetus of said pregnant subject is at said elevated risk of said pregnancy-related health condition. 
     
     
         30 . A method for monitoring a pregnant subject or a fetus of said pregnant subject, comprising:
 (a) obtaining a biological sample from said pregnant subject;   (b) sequencing nucleic acid molecules derived from said biological sample to identify a set of ribonucleic acid (RNA) transcripts in said biological sample; and   (c) analyzing said set of RNA transcripts identified in (b) to monitor a health of said pregnant subject or a health or developmental state of said fetus of said pregnant subject.