Patent US10325673

Deep transcriptomic markers of human biological aging and methods of determining a biological aging clock
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US10325673

1. A method of creating a biological aging clock for a subject, the method comprising: (9) (5)

(a) receiving a transcriptome signature derived from a tissue or organ of the subject;

(b) creating input vectors based on the transcriptome signature;

(d) generating a predicted biological aging clock of the tissue or organ based on the input vectors by the machine learning platform, wherein the biological aging clock is specific to the tissue or organ; and

(e) preparing a report that includes the biological aging clock that identifies a predicted biological age of the tissue or organ.

2. The method of claim 1, further comprising: (1) (2)

creating at least a second biological aging clock by repeating any one or more of steps (a), (b), (c), and/or (d), wherein the second biological aging clock is based on a transcriptome from the tissue or organ of the subject, a different tissue or organ of the subject or a tissue or organ of a second subject; and

optionally, preparing a report that includes the second biological aging clock that identifies a second predicted biological age of the tissue or organ of the subject, a different tissue or organ of the subject or a tissue or organ of a second subject.

3. The method of claim 2, further comprising: (1) (2)

combining the biological aging cock with the second biological aging clock to create a synthetic biological aging clock, wherein the synthetic biological aging clock provides a synthetic biological age of the tissue, organ, or of the subject; and

optionally, preparing a report that includes the synthetic biological aging clock that identifies the synthetic biological age of the tissue, organ, or of the subject.

4. The method of claim 3, further comprising one or more of: (0) (5)

comparing the predicted biological age of the tissue or organ with the actual age of the subject;

comparing the second predicted biological age of the tissue or organ with the actual age of the subject;

comparing the synthetic biological age of the tissue or organ and with the actual age of the subject,

wherein the method further comprises:

preparing a report with the comparing and with a difference from the actual age of the subject.

5. The method of claim 1, wherein the report includes one or more of: (1) (7)

a therapeutic regimen based on the predicted biological age in view of an actual age of the subject;

a diet regimen based on the predicted biological age in view of an actual age of the subject;

a questionnaire about lifestyle habits;

a prognosis of the life expectancy with and/or without the therapeutic regimen;

a prognosis of the life expectancy with and/or without the diet regimen;

a prognosis of the probability of survival of patient during the therapeutic regimen; or

a prognosis of the probability of survival of patient during the diet regimen.

7. The method of claim 5, wherein the therapeutic regimen includes one or more of: (1) (5)

applying a senoremediation drug treatment protocol to the subject in order to rescue one or more first cells in the subject;

applying a senolytic drug treatment protocol to the subject in order to remove one or more second cells in the subject;

introducing stem cells into a tissue and/or organ of the subject in order to rejuvenate one or more tissue cells in the tissue and/or one or more organ cells in the organ;

carrying out a reinforcement step that includes one or more actions that prevent further senescence or degradation of the tissue or organ; or

one or more actions that prevent further senescence or degradation of the tissue or organ is derived from the computational transcriptome analysis of the tissue or organ of the subject.

8. The method of claim 7, further comprising: (0) (4)

performing feature importance analysis for ranking genes or gene sets by their importance in age prediction; or

correlating a gene expression level with the predicted biological age of the subject;

identifying a subset of a genes or gene sets or biological pathways thereof that are selected as targets the therapeutic regimen;

correlating a biological signaling pathway signature with the predicted biological age of the subject.

6. The method of claim 1, wherein the tissue or organ are: (0) (6)

diseased;

healthy;

determined as susceptible to disease;

undergoing senescence;

in pre-senescence; or

non-senescent.

9. The method of claim 1, wherein the transcriptome signatures are based on signaling pathway activation signatures. (0)

10. The method of claim 1, after a defined time period, (0) (3)

11. The method of claim 1, further comprising: (0) (7)

performing a therapeutic regimen over a defined time period,

performing steps (a), (b), (c), (d), and (e) in a second iteration; and

comparing the initial report with the report of the second iteration;

determining a change in the predicted biological age over the defined time period; and

determining: whether the therapeutic regimen changed the predicted biological age,

if the therapeutic regimen changed the predicted biological age, then determine whether or not to: continue therapeutic regimen, change therapeutic regimen, or stop therapeutic regimen; or

if the therapeutic regimen does not change the predicted biological age, then determine whether or not to: continue therapeutic regimen, change therapeutic regimen, or stop therapeutic regimen.

12. The method of claim 1, further comprising performing one or more of: (0) (2)

13. The method of claim 1, further comprising performing one or more of (0) (3)

14. The method of claim 1, further comprising: (1) (2)

16. A computer program product comprising a tangible, non-transitory computer readable medium having a computer readable program code stored thereon, the code being executable by a processor to perform a method for biological aging clock for a patient, the method comprising: (4) (5)

(a) receiving a transcriptome signature derived from a tissue or organ of the subject;

(b) creating input vectors based on the transcriptome signature;

(e) preparing a report that includes the biological aging clock that identifies a predicted biological age of the tissue or organ.

17. The computer program product of claim 16, the method further comprising: (1) (2)

18. The computer program product of claim 17, the method further comprising: (0) (2)

19. The computer program product of claim 16, the method further comprising: (0) (5)

comparing the predicted biological age of the tissue or organ with the actual age of the subject;

comparing the second predicted biological age of the tissue or organ with the actual age of the subject;

comparing the synthetic biological age of the tissue or organ and with the actual age of the subject,

wherein the method further comprises:

preparing a report with the comparing and with a difference from the actual age of the subject.

20. The computer program product of claim 16, the method further comprising: (0) (4)

performing feature importance analysis for ranking genes or gene sets by their importance in age prediction;

correlating a gene expression level with the predicted biological age of the subject;

identifying a subset of a genes or gene sets or biological pathways thereof that are selected as targets the therapeutic regimen; or

correlating a biological signaling pathway signature with the predicted biological age of the subject.

21. The computer program product of claim 16, the method further comprising: (0) (4)

after a defined time period,

performing steps (a), (b), (c), (d), and (e) in a second iteration; and

comparing the initial report with the report of the second iteration; and

determining a change in the predicted biological age over the defined time period.

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Patent US10325673

Deep transcriptomic markers of human biological aging and methods of determining a biological aging clock

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