Automated DNA array segmentation and analysis
First Claim
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 a memory device;
(b) selecting a set of image information within said frame including a selected set of the DNA spot images;
(c) generating a grid in said memory device, the grid including a plurality of spaced grid points corresponding to said selected DNA spot images, each grid point including position information indicating the position of the grid point within said frame; and
(d) modifying a current position of at least one grid point corresponding to a spot image in said selected image, including the steps of;
(i) selecting a first bounding area in the frame around the current position of the grid point;
(ii) 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;
(iii) 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 one or more grid points around said grid point; and
(iv) 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.
1 Assignment
0 Petitions
Accused Products
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 diaplays 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.
-
Citations
94 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 a memory device;
(b) selecting a set of image information within said frame including a selected set of the DNA spot images;
(c) generating a grid in said memory device, the grid including a plurality of spaced grid points corresponding to said selected DNA spot images, each grid point including position information indicating the position of the grid point within said frame; and
(d) modifying a current position of at least one grid point corresponding to a spot image in said selected image, including the steps of;
(i) selecting a first bounding area in the frame around the current position of the grid point;
(ii) 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;
(iii) 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 one or more grid points around said grid point; and
(iv) 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. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21)
(a) a width substantially equal to the smaller of;
(i) the distance between the positions of the grid point in the image segment and the midpoint between said grid point and an adjacent grid point to the left of said grid point, and (ii) the distance between the positions of said grid point and the midpoint between said grid point and an adjacent grid point to the right of said grid point; and
(b) a height substantially equal to the smaller of;
(i) the distance between the positions of a said grid point and the midpoint between said grid point and an adjacent grid point to the left of said grid point, and (ii) the distance between the positions of said grid point and the midpoint between said grid point an adjacent grid point to the right of said grid point.
-
-
16. The method of claim 13, further comprising the step of quantifying at least a portion of image information in said image segment to obtain image characteristic values for said image segment.
-
17. The method of claim 16, 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.
-
18. The method of claim 16, wherein the frame image information includes a plurality of pixels each having an intensity level, and wherein the step of quantifying includes:
- (i) sorting all the pixel intensities within said image segment, (ii) selecting a portion of said pixels having intensities in a selected intensity range, (iii) computing the mean intensity value of pixels in said portion of the image segment, and (iv) reporting said mean value as an image characteristic value.
-
19. The method of claim 16, wherein the frame 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.
-
20. The method of claim 16, wherein the frame 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.
-
21. The method of claim 20 wherein step (i) further includes the steps of selecting said subset of said pixels in said image segment based at least on a spatial arrangement.
-
22. A software system for configuring a computer system comprising a processor, and a memory device, 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 the memory device;
(b) selecting a set of image information within said frame including a selected set of the DNA spot images;
(c) generating a grid in said memory device, the grid including a plurality of spaced grid points corresponding to said selected DNA spot images, each grid point including position information indicating the position of the grid point within said frame; and
(d) modifying a current position of at least one grid point corresponding to a spot image in said selected image, including the steps of;
(i) selecting a first bounding area in the frame around the current position of the grid point;
(ii) 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;
(iii) 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 one or more grid points around said gird point; and
(iv) 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. - View Dependent Claims (23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40)
(a) generate the grid having a two dimensional array of grid points; and
(b) select each image segment to include;
(1) a width substantially equal to the smaller of;
(ii) the distance between the positions of the grid point in the image segment and the midpoint between said grid point and an adjacent grid point to the left of said grid point, and (ii) the distance between the positions of said grid point and the midpoint between said grid point and an adjacent grid point to the right of said grid point; and
(2) a height substantially equal to the smaller of;
(i) the distance between the positions of a said grid point and the midpoint between said grid point and an adjacent grid point to the left of said grid point, and (ii) the distance between the positions of said grid point and the midpoint between said grid point an adjacent grid point to the right of said grid point.
-
-
35. The software system of claim 32, further comprising program instructions for quantifying at least a portion of image information in said image segment to obtain image characteristic values for said image segment.
-
36. The software system of claim 35, further including program instructions for quantifying such that 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.
-
37. The software system of claim 35, 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) sorting all the pixel intensities within said image segment, (ii) selecting a portion of said pixels having intensities in a selected intensity range, (iii) computing the mean intensity value of pixels in said portion of the image segment, and (iv) reporting said mean value as an image characteristic value.
-
38. The software system of claim 35, wherein the frame of image information includes a plurality of pixels each having an intensity level, and wherein the program instructions for quantifying further include program instructions for:
- (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.
-
39. The software system of claim 35, wherein the frame of image information includes a plurality of pixels each having an intensity level, and wherein the program instructions for quantifying further include program instructions:
- (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.
-
40. The software system of claim 39 wherein the program instructions for step (i) further include program instructions for selecting said subset of said pixels in said image segment based at least on a spatial arrangement.
-
41. A computer system 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 computer system comprising:
-
(b) means for selecting a set of image information within said frame including a selected set of the DNA spot images;
(c) means for generating a grid in a memory device, the grid including a plurality of spaced grid points corresponding to said selected DNA spot images, each grid point including position information indicating the position of the grid point within said frame; and
(d) means for modifying a current position of at least one grid point corresponding to a spot image in said selected image, including;
(i) means for selecting a first bounding area in the frame around the current position of the grid point;
(ii) means for 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;
(iii) means for 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 one or more grid points around sais grid point; and
(iv) means for 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. - View Dependent Claims (42, 43, 44, 45, 46, 47, 48, 49, 50, 51)
-
-
52. 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, wherein the current position of one or more of the grid points can be modified in relation to other grid points;
(d) modifying a current position of at least one grid point corresponding to a spot image in said selected image, by modifying the position information of said grid point, based on properties of one or more spot images to shift said grid point toward the corresponding spot image; and
(e) 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. - View Dependent Claims (53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75)
(a) a width substantially equal to the smaller of;
(i) the distance between the positions of the grid point in the image segment and the midpoint between said grid point and an adjacent grid point to the left of said grid point, and (ii) the distance between the positions of said grid point and the midpoint between said grid point and an adjacent grid point to the right of said grid point; and
(b) a height substantially equal to the smaller of;
(i) the distance between the positions of a said grid point and the midpoint between said grid point and an adjacent grid point to the left of said grid point, and (ii) the distance between the positions of said grid point and the midpoint between said grid point an adjacent grid point to the right of said grid point.
-
-
62. The method of claim 60, further comprising the step of quantifying at least a portion of image information in said image segment to obtain image characteristic values for said image segment.
-
63. The method of claim 62, 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.
-
64. The method of claim 62, wherein the frame 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.
-
65. The method of claim 62, wherein the frame 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.
-
66. The method of claim 65 wherein:
- step (i) further includes the steps of selecting said subset of said pixels in said image segment based at least on a spatial arrangement.
-
67. The method of claim 65 wherein:
- step (i) further includes the steps of selecting said subset of said pixels in said image segment from an enclosed region around the spot image, and step (iii) further includes the steps of computing said second image characteristic value as a function of intensities of at least a portion of pixels proximate the enclosed region.
-
68. The method of claim 60, wherein said segment area is a function of the spacing between said grid point and one or more neighboring grid points.
-
69. The method of claim 52, wherein the step of segmenting comprises the steps of segmenting the selected set of image information into a plurality of image segments corresponding to at least a number of the plurality of grid points in the grid, each image segment defining a segment area around a corresponding grid point and including a corresponding spot image with minimum distance from said grid point, said segment area being a function of the spacing between said grid point and one or more neighboring grid points, wherein each spot image is contained in a corresponding image segment.
-
70. The method of claim of claim 52, wherein the step of segmenting comprises the steps of 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 with minimum distance from said grid point, said segment area being a function of a spot image area.
-
71. The method of claim 52 wherein the position of eash grid point of said at least a number of the grid points approximates a position of a corresponding spot image in said frame.
-
72. The method of claim 52, wherein at least a number of the grid points have a spatial relationship with corresponding spot images.
-
73. The method of claim 52, wherein at least a number of the grid points have a predefined spatial relationship with corresponding spot images.
-
74. The method of claim 52, wherein at least a number of the grid points have a one-to-one relationship with corresponding spot images.
-
75. The method of claim 52, wherein the arrangement of at least a number of the grid points approximates the arrangement of a corresponding set of the spot images in said frame.
-
76. 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, wherein the current position of one or more of the grid points can be modified in relation to other grid points;
(d) modifying a current position of at least one grid point corresponding to a spot image in said selected image, by modifying the position information of said grid point, based on properties of one or more spot images to shift said grid point toward the corresponding spot image; and
(e) 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. - View Dependent Claims (77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94)
(a) generate said grid as a two dimensional array of grid points; and
(b) select each image segment to include;
(1) a width substantially equal to the smaller of;
(ii) the distance between the positions of the grid point in the image segment and the midpoint between said grid point and an adjacent grid point to the left of said grid point, and (ii) the distance between the positions of said grid point and the midpoint between said grid point and an adjacent grid point to the right of said grid point; and
(2) a height substantially equal to the smaller of;
(i) the distance between the positions of a said grid point and the midpoint between said grid point and an adjacent grid point to the left of said grid point, and (ii) the distance between the positions of said grid point and the midpoint between said grid point an adjacent grid point to the right of said grid point.
-
-
83. The software system of claim 76, wherein the program instructions for segmenting comprise program instructions for 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 with minimum distance from said grid point.
-
84. The software system of claim 76, further comprising program instructions for quantifying at least a portion of image information in said image segment to obtain image characteristic values for said image segment.
-
85. The software system of claim 84, further including program instructions for quantifying such that 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.
-
86. The software system of claim 83, wherein said segment area is a function of the spacing between said grid point and one or more neighboring grid points.
-
87. The software system of claim 84, 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.
-
88. The software system of claim 84, 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) 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.
-
89. The software system of claim 76, wherein the program instructions for segmenting comprise program instructions for 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 with minimum distance from said grid point, said segment area being a function of a spot image area.
-
90. The software system of claim 76 wherein the position of each grid point of said at least a number of the grid points approximates a position of a corresponding spot image in said frame.
-
91. The software system of claim 76, wherein at least a number of the grid points have a spatial relationship with corresponding spot images.
-
92. The software system of claim 76, wherein at least a number of the grid points have a predefined spatial relationship with corresponding spot images.
-
93. The software system of claim 76, wherein at least a number of the grid points have a one-to-one relation ship with corresponding spot images.
-
94. The software system of claim 76, wherein the arrangement of at least a number of the grid points approximates the arrangement of a corresponding set of the spot images in said frame.
Specification