Methods and models for post-operative recurrence in crohn's disease
AssigneeCedars-Sinai Medical Center
InventorsPhillip GU, Dermot P. MCGOVERN, Shishir DUBE
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Abstract
Provided herein are methods, systems, compositions and kits for modeling post-operative recurrence (POR) or postoperative prophylaxis persistence (POPP) in Crohn's disease patients. The present disclosure provides clinical, serologic, and genetic factors predictive of POR in patients with Crohn's disease. Also provided are clinical, serologic, and genetic factors predictive of POPP in Crohn's disease patients. The clinical, serologic, and genetic factors of the present disclosure are useful for selecting for prognosing, diagnosing, treatment, treating, monitoring a treatment, or optimizing a treatment for a Crohn's disease patient.
Claims153
A method of treating Crohn's disease (CD) in a subject, the method comprising:
- administering to the subject a therapeutically effective amount of a therapeutic agent for CD, wherein one or more post-operative prophylaxis persistence (“POPP”) markers were detected in the subject.
A method of determining prophylactic persistence of therapeutic agent in treating Crohn's disease (CD) in a subject that has undergone operation, the method comprising:
- a) detecting one or more post-operative prophylaxis persistence (“POPP”) markers in the subject;
- and
- b) determining a likelihood that the therapeutic agent exhibits the prophylactic persistence in treating the CD in the subject based, at least in part, on the one or more POPP markers detected in the subject, wherein the likelihood is compared with a control subject with the CD and that has received a surgical resection to treat the CD.
A method of treating Crohn's disease (CD) in a subject, the method comprising:
- administering to the subject a therapeutically effective amount of a therapeutic agent for treatment of the CD, wherein one or more post-operative recurrence (“POR”) markers were detected in the subject.
A method of determining the prognosis of post-operative recurrence (“POR”) of Crohn's disease (CD) in a subject, the method comprising:
- a) detecting one or more POR markers in the subject;
- and
- b) determining the subject to have a likelihood of POR based, at least in part on the one or more POR markers detected in the subject, relative to a control subject having the CD that has received a resection to treat the CD.
A method of enriching a target nucleic acid in a sample, the method comprising:
- a) providing a plurality of target nucleic acid sequences obtained from a biological sample from a subject with Crohn's disease (CD);
- b) bringing a fluid reaction formulation comprising a plurality of synthetic oligonucleotide molecules in contact with the plurality of target nucleic acid sequences, wherein each synthetic oligonucleotide molecule of the plurality of synthetic oligonucleotide molecules is complementary to at least one target nucleic acid sequence of the plurality of target nucleic acid sequences;
- c) hybridizing the plurality of synthetic oligonucleotide molecules to the plurality of synthetic oligonucleotide molecules;
- d) amplifying the plurality of target nucleic acid sequences hybridized to the plurality of synthetic oligonucleotide molecules in (c), thereby enriching the plurality of target nucleic acid sequences in the fluid reaction formulation;
- and
- e) detecting the plurality of target nucleic acid sequences that were enriched in (d), wherein the detecting in (e) of the plurality of target nucleic acid sequences is indicative of a high likelihood of post-operative prophylaxis persistence (“POPP”), as compared with a control subject.
A method of enriching a target nucleic acid in a sample, the method comprising:
- a) providing a plurality of target nucleic acid sequences obtained from a biological sample from a subject with Crohn's disease (CD);
- b) bringing a fluid reaction formulation comprising a plurality of synthetic oligonucleotide molecules in contact with the plurality of target nucleic acid sequences, wherein each synthetic oligonucleotide molecule of the plurality of synthetic oligonucleotide molecules is complementary to at least one target nucleic acid sequence of the plurality of target nucleic acid sequences;
- c) hybridizing the plurality of synthetic oligonucleotide molecules to the plurality of synthetic oligonucleotide molecules;
- d) amplifying the plurality of target nucleic acid sequences hybridized to the plurality of synthetic oligonucleotide molecules in (c), thereby enriching the plurality of target nucleic acid sequences in the fluid reaction formulation;
- and
- e) detecting the plurality of target nucleic acid sequences that were enriched in (d), wherein the detecting in (e) of the plurality of target nucleic acid sequences is indicative of a high likelihood of post-operative recurrence (“POR”) as compared with a control subject.
A computing platform for predicting a post-operative prophylaxis persistence (“POPP”) in a subject, the platform comprising:
- a) a genotyping device for determining genotype data of a subject with Crohn's disease (CD), wherein the subject is receiving a treatment for the CD comprising a therapeutic agent;
- and
- b) one or more computer processors operably coupled to the genotyping device, wherein the one or more computer processors are individually or collectively configured to perform operations comprising:
- i. receiving the genotype data from the genotyping device;
- and
- ii. identifying, in the genotype data, a genotype that is predictive of the POPP.
A computing platform for predicting a post-operative recurrence (“POR”) in a subject, the platform comprising:
- a) a genotyping device for determining genotype data of a subject with Crohn's disease (CD), wherein the subject is receiving a treatment for the CD comprising a therapeutic agent;
- and
- b) one or more computer processors operably coupled to the genotyping device, wherein the one or more computer processors are individually or collectively configured to perform operations comprising:
- i. receiving the genotype data from the genotyping device;
- and
- ii. identifying, in the genotype data, a predetermined genotype that is predictive of the POR.
A kit for predicting a post-operative prophylaxis persistence (“POPP”) in a subject having CD, the kit comprising:
- a) one or more detection agents configured to bind or hybridize to a polymorphism comprising an adenosine (“A”) at rs6811007 or a proxy polymorphism in linkage disequilibrium (LD) therewith as determined with an r2 of at least 0.85, or a combination thereof, or to bind or hybridize to a polymorphism comprising an adenosine (“A”) at a polymorphism position comprising rs1533236, or a proxy polymorphism position in linkage disequilibrium therewith as determined with an r2 of at least 0.85, or a combination thereof, or multiple detection agents configured to bind or hybridize to both;
- and
- b) instructions for use of the detection agent to detect an absence of the polymorphism or the proxy polymorphism in LD therewith in a sample obtained from the subject.
A kit for predicting a post-operative recurrence (“POR”) in a subject having CD, the kit comprising:
- a) one or more detection agent(s) configured to bind or hybridize to a polymorphism comprising an adenosine (“A”) at rs6811007, or a proxy polymorphism in linkage disequilibrium (LD) therewith as determined with an r2 of at least 0.85, or a combination thereof, configured to bind or hybridize to a polymorphism comprising an adenosine (“A”) at a polymorphism position comprising rs1533236, or a proxy polymorphism position in linkage disequilibrium therewith as determined with an r2 of at least 0.85, or a combination thereof, or multiple detection agents configured to bind or hybridize to both;
- and
- b) instructions for use of the detection agent to detect a presence of the polymorphism or the proxy polymorphism in LD therewith in a sample obtained from the subject.
Dependencies are inferred from the claim text.