IDENTIFICATION OF BIOMARKERS
The present invention relates to a method comprising the steps of obtaining a sample from the subject, measuring a plurality of biomolecules in the sample, identifying the measured biomolecules in the sample, characterized in that the method further comprises the steps of estimating a discriminatory ability of each measured biomolecule by using a paired test hypothesis, and integrating the estimated discriminatory abilities of the biomolecules into a kinetic analysis. More particularly, the present invention enables the use of such a method and a method for monitoring progress or treatment of a disease such as cardiovascular diseases. Such identification methods comprising the steps of obtaining a sample from the subject, measuring a plurality of biomolecules in the sample and identifying the measured biomolecules can particularly be used for monitoring progress or treatment of a disease.
1 . A method for identification of biomarkers in a subject, the method comprising:
obtaining a sample from the subject;
measuring a plurality of biomolecules in the sample;
identifying the measured biomolecules;
estimating a discriminatory ability of each identified biomolecule by using a paired test hypothesis; and
integrating estimated discriminatory abilities of the identified biomolecules into a kinetic analysis.
2 . The method according to claim 1 , further comprising searching significant correlations and kinetic relations between early-appearing and later-appearing biomolecules in serial sampling studies based on the kinetic analysis.
3 . The method according to claim 1 , wherein estimating the discriminatory ability of each identified biomolecule comprises identification and categorization of biomarker candidates according to their predictive value.
4 . The method according to claim 1 , wherein the paired test hypothesis is evaluated according to the formula:
pBI
=
λ
·
DA
*
·
Δ
change
CV
·
sign
(
Δ
change
)
with
Δ
change
=
{
Δ
if
Δ
≥
1
-
1
Δ
else
wherein pBI is an paired Biomarker Identifier, λ is a scaling factor, DA* is the initial measure DA rescaled between 0 and 1, CV is a coefficient of variation, sign( ) determines the direction of change, Δ change indicates changes in a biomolecule calculated as a relative increase or decrease from the levels of a reference cohort.
5 . The method according to claim 1 , wherein the discriminatory ability of each of the identified biomolecules is estimated by additionally using an unpaired test hypothesis.
6 . The method according to claim 5 , wherein the unpaired test hypothesis is evaluated according to the formula:
uBI
=
λ
·
TP
2
*
·
Δ
change
CV
ref
CV
·
sign
(
Δ
change
)
Δ
change
=
{
Δ
if
Δ
≥
1
-
1
Δ
else
with
Δ
ref
=
x
_
x
_
wherein uBI is an unpaired Biomarker Identifier, λ is a scaling factor, TP 2 * is an initial measure defined as TP 2 rescaled between 0 and 1, Δ change indicates changes in biomolecules calculated as a relative increase or decrease from the levels of a reference group, CV is a coefficient of variation, CV ref is a reference coefficient of variation, sign( ) determines the direction of change, x is the mean value from the levels of a biomolecule in a cohort, x ref is the mean value from the levels of a biomolecule in a reference cohort.
7 . The method according to claim 1 , wherein the biomolecules are selected from a group consisting of nucleotides, amino acids, organic acids, sugars, lipids, acyl-carnitines, peptides or proteins.
8 . The method according to claim 1 , wherein the sample comprises a body fluid or tissue.
9 . The method according to claim 8 , wherein the body fluid is blood and urine, blood or urine.
10 . A method of using biomarkers identified in a subject, the method comprising:
obtaining a sample from the subject;
measuring a plurality of biomolecules in the sample;
identifying the measured biomolecules;
estimating a discriminatory ability of each identified biomolecule by using a paired test hypothesis;
integrating estimated discriminatory abilities of the identified biomolecules into a kinetic analysis; and
predicting risk of future life threatening events in disease, prognosis or diagnosis based on the kinetic analysis.
11 . The method according to claim 10 , wherein disease is selected from the group consisting of metabolic diseases including cardiovascular disease or cancer.
12 . A method for monitoring progress or treatment of a disease, the method comprising:
(a) providing numerical scores for biomarkers based on the discriminatory ability by using the method according to claim 1 , wherein the scores are predetermined to be relevant to the disease;
(b) repeating (a) after a period of time during which subjects receive treatment for the disease, to obtain post-treatment scores;
(c) comparing the post-treatment scores from (b) with the scores from (a) versus scores for subjects not suffering under the disease, and
(d) classifying the treatment as being effective if scores from (b) are closer to the scores from (a) than to the scores for normal subjects.
13 . The method according to claim 12 , wherein the provision of numerical scores for biomarkers is carried out in at least one of a disease cohort versus a healthy cohort study and longitudinal biomarker cohort study.
14 . The method according to claim 12 , wherein the period of time is within a range of minutes, hours, days or months.
15 . The method according to claim 12 , wherein disease is selected from the group consisting of metabolic diseases including cardiovascular disease or cancer.