# US 12,008,755 B2 · Chromosomal enhancement and automatic detection of chromosomal abnormalities using chromosomal ideograms

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- Number: US 12,008,755 B2
- Document ID: US12008755B2
- Status: Granted
- Kind: B2
- Application number: 17/204,286
- Filed: 2021-03-17
- Published: 2021-09-23
- Granted: 2024-06-11
- Earliest claimed: 2020-03-17
- Assignees: National Guard Health Affairs; King Saud bin Abdulaziz University for Health Sciences; King Abdullah International Medical Research Center
- Applicants: National Guard Health Affairs; King Saud bin Abdulaziz University for Health Sciences; King Abdullah International Medical Research Center
- Inventors: Yahya Abdulfattah Bokhari; Areej Abdulaziz Alhareeri; Azizah Mohammed Alkhaldi; Abdulrhman Fahad Aljouie
- Web page: https://patentgrep.com/patent/US12008755B2

## CPC

- G06T 7/0014: {using an image reference approach}
- G06T 5/60: using machine learning, e.g. neural networks
- G06T 5/77: Retouching; Inpainting; Scratch removal
- G06T 5/80: Geometric correction
- G16B 20/20: Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
- G16B 40/20: Supervised data analysis
- G16B 45/00: ICT specially adapted for bioinformatics-related data visualisation, e.g. displaying of maps or networks
- G06T 5/70: Denoising; Smoothing
- G06T 2207/10056: Microscopic image
- G06T 2207/20081: Training; Learning
- G06T 2207/20084: Artificial neural networks [ANN]
- G06T 2207/30072: Microarray; Biochip, DNA array; Well plate
- G06T: IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY

## 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.

## Claims

### Claim 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.

### Claim 2 (depends on 1)

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.

### Claim 3 (depends on 1)

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.

### Claim 4 (depends on 1)

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.

### Claim 5 (depends on 1)

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.

### Claim 6 (depends on 1)

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.

### Claim 7 (depends on 1)

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.

### Claim 8 (depends on 1)

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

### Claim 9 (depends on 1)

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.

### Claim 10 (depends on 1)

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.

### Claim 11 (depends on 1)

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

### Claim 12 (depends on 1)

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.

### Claim 13 (depends on 1)

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.

### Claim 14 (depends on 1)

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).

### Claim 15 (depends on 1)

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

### Claim 16 (depends on 1)

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.

### Claim 17 (depends on 1)

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.

### Claim 18 (depends on 1)

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.

### Claim 19 (depends on 1)

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.

### Claim 20 (depends on 1)

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.