Pathogen biomarkers and uses therefor

A technology of biomarkers and indicators, applied in the field of diagnosis and/or monitoring of virus-related systemic inflammation, peripheral blood RNA and protein biomarkers, which can solve the problems of making decisions about the treatment and management of clinically diagnosed patients

Inactive Publication Date: 2018-09-07
IMMUNEXPRESS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Such confusion leads to difficulties in clinical diagnosis and in making decisions about subsequent patient treatment and management
Difficulties in clinical diagnosis are based on the following issues: 1) Given that many body organs / sites are infested with microorganisms (e.g. Escherichia coli in the gut, Staphylococcus epidermidis in the skin), viruses (e.g. what constitutes a "suspect" infection; 2) what constitutes a normal non-sterile body part Pathological growth of organisms? ;3) How viral / microbial / parasitic co-infections in non-sterile body parts (e.g., upper respiratory tract) contribute to SIRS, and if such infections are suspected the patient should be treated with antibiotics, anti-fungal, antiviral or Antiparasitic compounds?
The IgM / IgG ratio approach is also limited by the fact that the clinician must know a priori which specific test to order

Method used

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  • Pathogen biomarkers and uses therefor
  • Pathogen biomarkers and uses therefor
  • Pathogen biomarkers and uses therefor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0198] Group A biomarkers and their diagnostic performance across multiple data sets

[0199] Three separate biomarkers were found to have strong diagnostic performance across all virus data sets (as measured using area under the curve (AUC)). The three separate biomarkers include ZBP1 (DNA SEQ ID NO: 399) , TMEM62 (DNA SEQ ID NO: 414) and CD38 (DNA SEQ ID NO: 415). Four "core virus" data sets (including dengue fever, Lassa fever, influenza and herpes virus infection) were used to discover these biomarkers. Then ten "validating viruses" data sets are used to validate these biomarkers. These data sets include samples collected from patients suffering from a wide range of viral infections, including adenovirus, herpes virus, enterovirus, rhinovirus, hepatitis C virus, measles, rotavirus, and respiratory syncytial virus. The "non-viral inflammation" dataset includes conditions that cause systemic inflammation, including, among others, bacterial infections, allergic reactions, and ...

Embodiment 2

[0201] Groups B, C, D and E biomarkers. Group the biomarkers based on their correlation with ISG15, IL16, OASL and CD97

[0202] Two pairs of derived biomarkers (IL16 / ISG15; CD97 / OASL) were found to provide the highest AUC across all virus data sets studied. Then AUC will be provided> 0.8 (see Table 13 for the complete list of derived biomarkers) as ratio biomarkers based on their correlation with ISG15 (group B), IL16 (group C), OASL (group D) or CD97 (group E) Sex (as presented in Table 10) was assigned as a separate biomarker to one of the four groups.

Embodiment 3

[0204] VASIRS biomarker export (individual and exported biomarkers)

[0205] An illustrative process for identifying VaSIRS biomarkers for use in diagnostic algorithms will now be described.

[0206] Gene expression data (from clinical trials conducted by the inventors or from Gene Expression Omnibus) were analyzed using various statistical methods to identify individual and derived biomarkers (ratio), but mainly followed the method described in WO2015 / 117204. The individual and derived markers are ranked based on performance (area under the curve).

[0207] The data set used for training is derived from GEO (all comply with MIAME) and has the following limitations: use peripheral blood samples, use appropriate controls, use appropriate number of samples to provide significance after adjusting for false discovery rate (FDR), all The data passed standard quality control measures, and the principal component analysis did not show any artifacts or potential bias. The data set is divid...

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Abstract

Disclosed are compositions, methods and apparatus for diagnosing and/or monitoring a virus-associated systemic inflammation by measurement of a host immune response. The invention can be used for diagnosis including early diagnosis, monitoring, making treatment decisions, or management of subjects suspected of having systemic inflammation associated with an infection. More particularly, the present disclosure relates to peripheral blood RNA and protein biomarkers that are useful for specifically distinguishing between the host systemic immune response to viruses as compared to the host immuneresponse to other causes of systemic inflammation.

Description

Invention field [0001] This application claims the priority of Australian Provisional Application No. 2015903986 entitled "Pathogen biomarkers and usestherefor" filed on September 30, 2015, the content of which is incorporated herein by reference in its entirety. [0002] The present invention generally relates to compositions, methods and devices for diagnosing and / or monitoring virus-related systemic inflammation by measuring the host immune response. The present invention can be used for diagnosis, including early diagnosis, monitoring, treatment decision or management of subjects suspected of having systemic inflammation associated with infection. More particularly, the present invention relates to peripheral blood RNA and protein biomarkers, which are useful for specifically distinguishing the host's systemic immune response to viruses from the host's immune response to other causes of systemic inflammation. Background of the invention [0003] Fever and clinical signs of sys...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/686G01N33/50
CPCG01N33/6893C12Q2600/158G01N2800/26C12Q1/701C12Q1/6883C12Q1/70C12Q2600/106
Inventor 理查德·布鲁斯·布兰登布莱恩·安德鲁·福克斯里奥·查尔斯·麦克休黛尔·罗兰·桑普森
Owner IMMUNEXPRESS
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