Chromosomal enhancement and automatic detection of chromosomal abnormalities using chromosomal ideograms

Patent metadata

Field	Value
Publication number	US-12008755-B2
Application number	US-202117204286-A
Country	US
Kind code	B2
Filing date	Mar 17, 2021
Priority date	Mar 17, 2020
Publication date	Jun 11, 2024
Grant date	Jun 11, 2024

Abstract

A method for detecting chromosomal abnormalities comprising conversion of a chromosomal image into an ideogram which is compared to a control or standard ideogram of a chromosome; or converting an ideogram of a chromosome into a chromosomal image.

First claim

The invention claimed is:

1. A computer-implemented method for detecting chromosomal abnormalities cryptic deletions or putative cryptic deletions comprising:
obtaining an image of a banding pattern of a chromosome comprising a cryptic deletion or putative cryptic deletion,
converting the image into an ideogram depicting said banding pattern,
comparing the ideogram to an ideogram of an image of a paired control chromosome not comprising the cryptic deletion or putative cryptic deletion, and
identifying a difference in a banding pattern between the ideogram of the chromosome and the ideogram of the paired control chromosome,
wherein said difference indicates a cryptic deletion or putative cryptic deletion in the imaged chromosome.

2. The method of claim 1 ,
wherein the obtaining an image of a banding pattern of a chromosome comprises obtaining an image of a chromosome containing a cryptic deletion and an image of a paired control chromosome not containing the cryptic deletion,
wherein the converting the image into an ideogram depicting said banding pattern comprises converting images of the chromosome and its paired control chromosome into ideograms, and
wherein the identifying the difference in a banding pattern comprises identifying a difference between the ideogram of the chromosome containing the cryptic deletion and the ideogram of the second paired chromosome not containing the cryptic deletion,
wherein the comparing of the ideogram to an ideogram of the paired control chromosome not comprising the cryptic deletion comprises comparing the banding pattern of the ideogram of the chromosome containing the cryptic deletion to the banding pattern of the ideogram of its paired chromosome not containing the cryptic deletion, thereby identifying the cryptic deletion.

3. The method of claim 1 , wherein the converting an image of the chromosome comprising the cryptic deletion into an ideogram is performed manually using a subset of chromosome images thereby creating a paired set of chromosomes and ideograms which are used to train a model.

4. The method of claim 1 , wherein the converting an image of the chromosome comprising the cryptic deletion into an ideogram comprises passing an image of the chromosome through a function that outputs an ideogram corresponding to the chromosomal image.

5. The method of claim 1 , wherein the converting an image of a chromosome comprising the cryptic deletion into an ideogram comprises using CycleGAN with random, software-generated chromosomal ideograms, which have random bands, and then bending or curving the random shapes to mimic natural bends and curves in the chromosome image using polynomial, sine and cosine functions.

6. The method of claim 1 , wherein the converting an image of the chromosome comprising the cryptic deletion into an ideogram comprises image-to-image translation or pix2pix translation with handmade labeling which precisely or exactly mimics shapes of curved and bent bands in a chromosome.

7. The method of claim 1 , further comprising staining a metaphase chromosome to form a banding pattern on the chromosome comprising the cryptic deletion and photographing or scanning the banding pattern to produce the image of a chromosome prior to converting said image into an ideogram.

8. The method of claim 1 , further comprising autoclassifying the chromosome comprising the cryptic deletion as normal, abnormal, or potentially abnormal.

9. The method of claim 1 , further comprising generating or providing computer-generated text describing one or more chromosomal abnormalities or putative abnormalities comprising the cryptic deletion.

10. The method of claim 1 , further comprising enhancing the chromosome image of the chromosome comprising the cryptic deletion without adding or deleting information prior to converting the image into an ideogram.

11. The method of claim 1 , in which all chromosomes in a subject's karyotype are converted to ideograms.

12. The method of claim 1 , further comprising converting the chromosome ideogram into an image of a real chromosome to confirm the chromosomal bands with respect to banding in a standard ISCN ideogram.

13. The method of claim 1 , wherein the ideogram of the paired control chromosome is a normal human chromosome and/or wherein the ideogram of the paired control chromosome is of an abnormal human chromosome comprising the cryptic deletion.

14. The method of claim 1 , wherein the ideogram of the paired control chromosome is described by the International System for Human Cytogenetic Nomenclature (ISCN-2005).

15. The method of claim 1 , further comprising producing a karyotype of chromosomes in the sample comprising the cryptic deletion.

16. The method of claim 1 , wherein said identifying employs the ideogram to further identify an exact break point of a chromosome, to further identify a chromosomal duplication, to further identify a chromosomal inversion, or to further identify a chromosomal translocation.

17. The method of claim 1 , wherein the control ideogram of the paired control chromosome is obtained from a chromosome paired with the chromosome containing the cryptic deletion.

18. The method of claim 1 , wherein obtaining an image of a banding pattern of a chromosome comprising a cryptic deletion comprises obtaining images from multiple chromosomes in a karyotype.

19. The method of claim 1 , further comprising treating the subject for a disease, disorder, or condition associated with the chromosome identified as containing the cryptic deletion.

20. The method of claim 1 , wherein the identifying a difference in a banding pattern of a chromosome comprises manual visual inspection of the ideogram containing a cryptic deletion or putative cryptic deletion and the paired control ideogram or evaluation of the ideogram and paired control ideogram using artificial intelligence.

Assignees

• Nat Guard Health Affairs
• King Saud Bin Abdulaziz Univ For Health Sciences
• King Abdullah International Medical Res Center

Inventors

• Bokhari Yahya Abdulfattah
• Alhareeri Areej Abdulaziz
• Alkhaldi Azizah Mohammed
• Aljouie Abdulrhman Fahad

Classifications

• G06T5/70

  Denoising; Smoothing · CPC title

• G06T2207/10056

  Microscopic image · CPC title

• G06T5/80

  Geometric correction · CPC title

• G16B20/20 Primary

  Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection · CPC title

• G06T2207/20081

  Training; Learning · CPC title