Automated DNA array image segmentation and analysis

• US 20040047499A1
• Filed: 09/10/2003
• Published: 03/11/2004
• Est. Priority Date: 02/07/1998
• Status: Active Grant

• Current Assignee: Biodiscovery Inc. (BioNano Genomics, Inc.)
• Original Assignee: Biodiscovery Inc. (BioNano Genomics, Inc.)
• Inventors: Shams, Soheil
• Granted Patent: US 6,990,221 B2
• Time in Patent Office: Days
• US Class Current: 382/129
• CPC Class Codes: G06T 2207/10056 Microscopic image
• CPC Class Codes: G06T 2207/10064 Fluorescence image
• CPC Class Codes: G06T 2207/30072 Microarray; Biochip, DNA array; Well plate
• CPC Class Codes: G06T 7/0012 Biomedical image inspection
• CPC Class Codes: G06T 7/11 Region-based segmentation
• CPC Class Codes: G06T 7/75 involving models

Abstract

A segmentation method of a frame of image information including a plurality of spaced DNA spot images corresponding to a plurality of DNA spots. The image information includes image intensity level information corresponding to said DNA spots. The frame is stored in a memory device and a set of image information within said frame including a selected set of the DNA spot images is selected. A grid including a plurality of spaced grid points corresponding to said selected DNA spot images is generated, such that each grid point includes position information indicating the position of the grid point within said frame. The current position of one or more grid points are adjusted by: selecting a first bounding area in the frame around the current position of the grid point; generating a first position update including position information for updating a current position of said grid point to a first new position within the first bounding area, the location of said first new position relative to said current position being a function of intensity level of at least a portion of the image within the first bounding area; generating a second position update including position information for updating said current position to a second new position in the frame, said second new position being in a geometric arrangement with the position of grid points around said grid point; and updating said current position with the position information of the first and the second position updates, thereby shifting said grid point toward the corresponding spot image. A display method displays image information corresponding to a plurality of DNA spot images of at least one DNA spot, the image information including image characteristic values including background and signal intensity levels. For each DNA spot image: (1) background and signal intensity levels are extracted from the image characteristic values for the spot image, and (2) difference values between the background intensity levels and signal intensity levels are determined. For each DNA spot: (1) the corresponding difference values are related a range of graphic values, (2) a graphic value for each difference value is selected; and (3) the selected graphic values are displayed.

Claims

1. A method for segmentation of a frame of image information including a plurality of spaced DNA spot images corresponding to a plurality of DNA spots, said image information including image intensity level information corresponding to said DNA spots, the method comprising the steps of:

(a) storing the frame of image information in memory;

(b) selecting a set of image information within said frame including a selected set of the DNA spot images;

(c) generating a grid in memory, the grid including a plurality of spaced grid points corresponding to said selected set of DNA spot images, the grid points having a predefined relationship, each grid point including position information indicating the position of the grid point within said image frame;

(d) segmenting the selected set of image information by selecting at least one image segment defining a segment area around a grid point and including a spot image; and

(e) quantifying at least a portion of image information in said image segment to obtain image characteristic values for said image segment.

2. The method of claim 1, wherein said segment area is a function of the spacing between said grid point and one or more neighboring grid points.

3. The method of claim 1, wherein the image characteristic values include DNA information for a DNA spot corresponding to the DNA spot image in said image segment, said DNA information including gene expression values.

4. The method of claim 1, wherein the frame of image information includes a plurality of pixels each having an intensity level, and wherein the step of quantifying includes:

(i) sorting at least a portion of the pixel intensities within said image segment, (ii) selecting a portion of said pixels, and (iii) computing an image characteristic value for the selected pixel values as function of the intensities of at least a portion of the selected pixel values.

5. The method of claim 1, wherein the frame of image information includes a plurality of pixels each having an intensity level, and wherein the step of quantifying includes:

(i) selecting a subset of said pixels in said image segment, (ii) computing a first image characteristic value as a function of at least a portion of the intensities of the selected pixel values, and (iii) computing a second image characteristic value as a function of intensities of at least a portion of pixels proximate said subset of pixels.

6. A software system for configuring a computer system comprising a processor, and memory, for segmentation of a frame of image information including a plurality of spaced DNA spot images corresponding to a plurality of DNA spots, said image information, including image intensity level and intra frame position information corresponding to said DNA spots, the software system comprising program instructions for:

(a) storing the frame of image information in memory;

(b) selecting a set of image information within said frame including a selected set of the DNA spot images;

(c) generating a grid in memory, the grid including a plurality of spaced grid points corresponding to said selected set of DNA spot images, the grid points having a predefined relationship, each grid point including position information indicating the position of the grid point within said image frame;

(d) segmenting the selected set of image information by selecting at least one image segment defining a segment area around a grid point and including a spot image; and

(e) quantifying at least a portion of image information in said image segment to obtain image characteristic values or said image segment.

7. The software system of claim 6, wherein said segment area is a function of the spacing between said grid point and one or more neighboring grid points.

8. The software system of claim 6, wherein said image characteristic values include DNA information for a DNA spot corresponding to the DNA spot image in said image segment, said DNA information including gene expression values.

9. The software system of claim 6, wherein the frame of image information includes a plurality of pixels each having an intensity level, and wherein the program instructions for quantifying include program instructions for:

(i) sorting all the pixel intensities within said image segment, (ii) selecting a portion of said pixels, (iii) computing an image characteristic value for the selected pixel values as function of the intensities of at least a portion of the selected pixel value.

10. The software system of claim 6, wherein the frame image information includes a plurality of pixels each having an intensity level, and wherein the program instructions for quantifying include program instructions for:

(i) selecting a subset of said pixels in said image segment, (ii) computing a first image characteristic value as a function of at least a portion of the intensities of the selected pixel values, and (iii) computing a second image characteristic value as a function of intensities of at least a portion of pixels proximate said subset of pixels.