阅读说明：本技术 一种自动化数据处理以及作图方法及系统 (Automatic data processing and mapping method and system ) 是由 李冬梅 喻长顺 蔡春泉 舒剑波 陈建春 贾晓冬 于 2021-06-21 设计创作，主要内容包括：本发明提出了一种自动化数据处理以及作图方法及系统,包括：步骤S1,采用计算机编程语言对数据的自动化处理预设逻辑,包括：(1)根据预设的CNV变异类型拆分数据；(2)获取注释文件,所述注释文件中记载有待处理的目标数据,对注释文件中目标数据的归一化值z得分大于第一预设值的绝对值,自定义致病性风险的变异；(3)获取注释文件,所述注释文件中记载有待处理的目标数据,对注释文件中目标数据的拷贝数CopyNum小于等于第二预设值,自定义致病性风险的变异；(4)删除预设列名的列；(5)根据染色体对文件进行拆分：为匹配R程序将重复变异类型和缺失变异类型分别按照染色体进行拆分,并分别命名；步骤S2,自动化绘制svg格式的矢量图和pdf图。(The invention provides an automatic data processing and mapping method and system, which comprises the following steps: step S1, adopting computer programming language to automatically process preset logic of data, including: (1) splitting data according to a preset CNV variation type; (2) acquiring an annotation file, wherein target data to be processed are recorded in the annotation file, the score of a normalized value z of the target data in the annotation file is larger than the absolute value of a first preset value, and the variation of the pathogenicity risk is customized; (3) acquiring an annotation file, wherein target data to be processed are recorded in the annotation file, and the variation of pathogenicity risk is customized when the copy number CopyNum of the target data in the annotation file is less than or equal to a second preset value; (4) deleting the columns with preset column names; (5) splitting the file according to chromosomes: splitting the repeated variation type and the missing variation type according to chromosomes respectively for matching the R program, and naming the split repeated variation type and the missing variation type respectively; and step S2, automatically drawing the vector diagram and pdf diagram in the svg format.)

1. An automated data processing and mapping method, comprising the steps of:

step S1, adopting computer programming language to automatically process preset logic of data, including:

(1) splitting data according to a preset CNV variation type;

(2) acquiring an annotation file, wherein target data to be processed are recorded in the annotation file, the score of a normalized value z of the target data in the annotation file is larger than the absolute value of a first preset value, and the variation of the pathogenicity risk is customized;

(3) obtaining an annotation file, wherein target data to be processed are recorded in the annotation file, and the copy number CopyNum of the target data in the annotation file is less than or equal to a second preset value, so that the variation of pathogenic risks is customized; wherein the copy number in the human genome is up to 4 copies;

(4) deleting the columns with preset column names;

(5) splitting the file according to chromosomes: splitting the repeated variation type and the missing variation type according to chromosomes respectively for matching the R program, and naming the split repeated variation type and the missing variation type respectively;

and step S2, automatically drawing the vector diagram and pdf diagram in the svg format.

2. The automated data processing and mapping method of claim 1, wherein the predetermined CNV variant types comprise: deletion variations and repeat variations.

3. The automated data processing and mapping method of claim 1, wherein the preset column names comprise: "CnvName", "start _ bin", "end _ bin", "cnv _ length", "continue _ bin _ num", "bin _ num", "raito", "z-score", "Tag", "cytoBand", "gene", "OMIM", "decipher", "DGV".

4. The automated data processing and mapping method of claim 1, wherein the matching R procedure entails chromosome splitting of repeated variant types, named dup1.txt ", and chromosome splitting of deleted variant types, named indel1. txt".

5. The automated data processing and mapping method of claim 1, wherein in step S2, a plurality of chromosomes are first placed in groups, wherein the first group is chromosomes 1-3, the second group is chromosomes 4-5, the third group is chromosomes 6-12, the fourth group is chromosomes 13-15, the fifth group is chromosomes 16-18, the sixth group is chromosomes 19-20, the seventh group is chromosomes 21-22, and the eighth group is female X chromosome/male X-Y chromosome;

then, carrying out equal scaling on the chromosome; according to the color and the serial number of the novel marking bands of the chromosome bands, marking the centromere locus of the chromosome according to the centromere position of the chromosome; drawing a scale on the right side of the chromosome, and respectively substituting the data of the repeated mutation type and the data of the missing mutation type into the map to generate a vector map and a pdf map in an svg format;

drawing 24 chromosomes from a male sample, comprising: 22 autosomes + X chromosome + Y chromosome;

drawing 23 chromosomes from the female sample, including: 22 autosomes + X chromosomes, female sample X chromosomes had no dup.

6. An automated data processing and mapping system, comprising: a data automation processing module and an automation drawing module, wherein,

the data automated processing module is used for adopting a computer programming language to automatically process the data to preset logic, and comprises the following steps: (1) splitting data according to a preset CNV variation type;

(2) acquiring an annotation file, wherein target data to be processed are recorded in the annotation file, the score of a normalized value z of the target data in the annotation file is larger than the absolute value of a first preset value, and the variation of the pathogenicity risk is customized;

(3) obtaining an annotation file, wherein target data to be processed are recorded in the annotation file, and the copy number CopyNum of the target data in the annotation file is less than or equal to a second preset value, so that the variation of pathogenic risks is customized; wherein the copy number in the human genome is up to 4 copies;

(4) deleting the columns with preset column names;

(5) splitting the file according to chromosomes: splitting the repeated variation type and the missing variation type according to chromosomes respectively for matching the R program, and naming the split repeated variation type and the missing variation type respectively;

the automatic drawing module is used for automatically drawing the vector diagram and the pdf diagram in the svg format.

7. The automated data processing and diagramming system of claim 6, wherein the data automation processing module setting the predetermined CNV variation type includes: deletion variations and repeat variations.

8. The automated data processing and diagramming system of claim 6 wherein the predetermined column names comprise: "CnvName", "start _ bin", "end _ bin", "cnv _ length", "continue _ bin _ num", "bin _ num", "raito", "z-score", "Tag", "cytoBand", "gene", "OMIM", "decipher", "DGV".

9. The automated data processing and mapping system of claim 6, wherein the data automation processing module matches the R program requires splitting repeated variant types by chromosome, named dup1.txt ", splitting missing variant types by chromosome, named indel1. txt".

10. The automated data processing and mapping system of claim 6, wherein the automated mapping module first places a plurality of chromosomes in groups, wherein the first group is chromosomes 1-3, the second group is chromosomes 4-5, the third group is chromosomes 6-12, the fourth group is chromosomes 13-15, the fifth group is chromosomes 16-18, the sixth group is chromosomes 19-20, the seventh group is chromosomes 21-22, and the eighth group is female X chromosome/male X-Y chromosome;

then, carrying out equal scaling on the chromosome; according to the color and the serial number of the novel marking bands of the chromosome bands, marking the centromere locus of the chromosome according to the centromere position of the chromosome; drawing a scale on the right side of the chromosome, and respectively substituting the data of the repeated mutation type and the data of the missing mutation type into the map to generate a vector map and a pdf map in an svg format;

drawing 24 chromosomes from a male sample, comprising: 22 autosomes + X chromosome + Y chromosome;

drawing 23 chromosomes from the female sample, including: 22 autosomes + X chromosomes, female sample X chromosomes had no dup.

Technical Field

The invention relates to the technical field of image data processing, in particular to an automatic data processing and plotting method and system.

Background

High-Throughput Sequencing (also known as Next-Generation Sequencing) is one of the gene Sequencing technologies, and is typically characterized in that thousands of genes can be detected at a time, and compared with one-Generation Sequencing, that is, Sanger Sequencing can only detect hundreds of bases at a time, a large amount of data can be generated by greatly increasing the number of bases. And annotating the generated data by a bioinformatics method to generate a variation annotation table. Currently, the high throughput sequencing technology is widely applied to whole exome sequencing to detect about 2 ten thousand genes, wherein Copy Number Variation (CNV) is an important component of Structural Variation (SV) of a gene, and is caused by genome rearrangement, generally refers to increase or decrease of Copy Number of large genomic fragments with length of 1kb or more, and mainly shows deletion (deletion) and duplication (duplication) at a sub-microscopic level. Each clinical sample analysis requires analysis of two variants from different angles, and a great deal of time and effort is required to manually analyze the samples in the face of a large number of clinical samples.

Disclosure of Invention

The object of the present invention is to solve at least one of the technical drawbacks mentioned.

To this end, the invention proposes an automated data processing and mapping method.

In order to achieve the above object, an embodiment of the present invention provides an automated data processing and plotting method, including the steps of:

step S1, adopting computer programming language to automatically process preset logic of data, including:

(1) splitting data according to a preset CNV variation type;

(2) acquiring an annotation file, wherein target data to be processed are recorded in the annotation file, the score of a normalized value z of the target data in the annotation file is larger than the absolute value of a first preset value, and the variation of the pathogenicity risk is customized;

(3) obtaining an annotation file, wherein target data to be processed are recorded in the annotation file, and the copy number CopyNum of the target data in the annotation file is less than or equal to a second preset value, so that the variation of pathogenic risks is customized; wherein the copy number in the human genome is up to 4 copies;

(4) deleting the columns with preset column names;

(5) splitting the file according to chromosomes: splitting the repeated variation type and the missing variation type according to chromosomes respectively for matching the R program, and naming the split repeated variation type and the missing variation type respectively;

and step S2, automatically drawing the vector diagram and pdf diagram in the svg format.

Further, the predetermined CNV variation types include: deletion variations and repeat variations.

Further, the preset column names include: "CnvName", "start _ bin", "end _ bin", "cnv _ length", "continue _ bin _ num", "bin _ num", "raito", "z-score", "Tag", "cytoBand", "gene", "OMIM", "decipher", "DGV".

Further, the match R program requires splitting repeated variant types by chromosome, named as "dup 1. txt", and splitting deleted variant types by chromosome, named as "indel 1. txt".

Further, in the step S2, firstly, a plurality of chromosomes are placed in groups, wherein the first group is chromosomes 1-3, the second group is chromosomes 4-5, the third group is chromosomes 6-12, the fourth group is chromosomes 13-15, the fifth group is chromosomes 16-18, the sixth group is chromosomes 19-20, the seventh group is chromosomes 21-22, and the eighth group is female X chromosome/male X-Y chromosome;

then, carrying out equal scaling on the chromosome; according to the color and the serial number of the novel marking bands of the chromosome bands, marking the centromere locus of the chromosome according to the centromere position of the chromosome; drawing a scale on the right side of the chromosome, and respectively substituting the data of the repeated mutation type and the data of the missing mutation type into the map to generate a vector map and a pdf map in an svg format;

drawing 24 chromosomes from a male sample, comprising: 22 autosomes + X chromosome + Y chromosome;

drawing 23 chromosomes from the female sample, including: 22 autosomes + X chromosomes, female sample X chromosomes had no dup.

The embodiment of the invention also provides an automatic data processing and plotting system, which comprises: a data automation processing module and an automation drawing module, wherein,

the data automated processing module is used for adopting a computer programming language to automatically process the data to preset logic, and comprises the following steps: (1) splitting data according to a preset CNV variation type;

(2) acquiring an annotation file, wherein target data to be processed are recorded in the annotation file, and the variation of the pathogenicity risk is customized for the normalized value of the target data in the annotation file and the absolute value of the z score which is greater than a first preset value;

(3) obtaining an annotation file, wherein target data to be processed are recorded in the annotation file, and the copy number CopyNum of the target data in the annotation file is less than or equal to a second preset value, so that the variation of pathogenic risks is customized; wherein the copy number in the human genome is up to 4 copies;

(4) deleting the columns with preset column names;

(5) splitting the file according to chromosomes: splitting the repeated variation type and the missing variation type according to chromosomes respectively for matching the R program, and naming the split repeated variation type and the missing variation type respectively;

the automatic drawing module is used for automatically drawing the vector diagram and the pdf diagram in the svg format.

Further, the setting of the preset CNV variation type by the data automation processing module includes: deletion variations and repeat variations.

Further, the preset column names include: "CnvName", "start _ bin", "end _ bin", "cnv _ length", "continue _ bin _ num", "bin _ num", "raito", "z-score", "Tag", "cytoBand", "gene", "OMIM", "decipher", "DGV".

Further, the data automation processing module matching R program needs to split the repeated variant type by chromosome, named in the form of dup1.txt, split the deletion variant type by chromosome, named in the form of indel1. txt.

Further, the automatic drawing module firstly arranges a plurality of chromosomes in groups, wherein the first group is chromosomes 1-3, the second group is chromosomes 4-5, the third group is chromosomes 6-12, the fourth group is chromosomes 13-15, the fifth group is chromosomes 16-18, the sixth group is chromosomes 19-20, the seventh group is chromosomes 21-22, and the eighth group is female X chromosome/male X-Y chromosome;

then, carrying out equal scaling on the chromosome; according to the color and the serial number of the novel marking bands of the chromosome bands, marking the centromere locus of the chromosome according to the centromere position of the chromosome; drawing a scale on the right side of the chromosome, and respectively substituting the data of the repeated mutation type and the data of the missing mutation type into the map to generate a vector map and a pdf map in an svg format;

drawing 24 chromosomes from a male sample, comprising: 22 autosomes + X chromosome + Y chromosome;

drawing 23 chromosomes from the female sample, including: 22 autosomes + X chromosomes, female sample X chromosomes had no dup.

The core of the method and the system for automatically processing data and drawing the graph is to automatically process the data and automatically draw a vector diagram and a pdf diagram in an svg format by adopting a computer programming language (such as a python program). Specifically, by combining python program data processing and R program visual mapping, a clinical sample can be processed in a few minutes, the position of the repeat and deletion variation of a large segment on a chromosome and the size of the repeat and deletion variation can be quickly and accurately found, all the repeat and deletion variation can be clearly seen, the working efficiency is greatly improved, and the clinical interpretation can be better served. The software capable of rapidly processing data and drawing developed by the invention can rapidly and accurately realize the filtering and splitting of clinical samples within 1 minute through the preset logic, greatly improve the efficiency, and can automatically draw vector diagrams and pdf diagrams in an svg format within 2 minutes by bringing the processed data into an R program, thereby greatly improving the working efficiency of clinical unscrambler.

Additional aspects and advantages of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention.

Drawings

The above and/or additional aspects and advantages of the present invention will become apparent and readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings of which:

FIG. 1 is a flow diagram of an automated data processing and mapping method according to an embodiment of the present invention;

FIG. 2 is a block diagram of an automated data processing and diagramming system according to an embodiment of the present invention;

FIG. 3 is a vector diagram of the svg format of a male X-Y chromosome implemented using the mapping method of the present invention;

fig. 4 is a vector diagram of the svg format of female X chromosome realized by the mapping method of the present invention.

Detailed Description

Reference will now be made in detail to embodiments of the present invention, examples of which are illustrated in the accompanying drawings, wherein like or similar reference numerals refer to the same or similar elements or elements having the same or similar function throughout. The embodiments described below with reference to the drawings are illustrative and intended to be illustrative of the invention and are not to be construed as limiting the invention.

As shown in FIG. 1, the logic set by the automated data processing and mapping method of the embodiment of the invention respectively considers two varieties of deletion and duplication, and innovatively adopts python processing data and an R mapping mode to analyze data of CNV.

Specifically, the automatic data processing and mapping method of the invention comprises the following steps:

step S1, adopting computer programming language to automatically process preset logic of data, including:

(1) splitting data according to a preset CNV variation type;

in an embodiment of the present invention, the predetermined CNV variation types include: deletion variations and repeat variations. The computer programming language can adopt python program or c + + and other programming languages.

(2) Obtaining an annotation file, wherein target data to be processed are recorded in the annotation file, the normalized value z score (standard value z-score) of the target data in the annotation file is larger than the absolute value of a first preset value, and the comprehensive consideration of laboratory self definition is the variation of pathogenicity risk.

Preferably, the first preset value is 3. It should be noted that the above values are only selected for the purpose of illustration, and are not intended to limit the present invention, and other values may be selected as needed.

(3) Obtaining an annotation file, wherein target data to be processed are recorded in the annotation file, and the copy number CopyNum of the target data in the annotation file is less than or equal to a second preset value, so that the variation of pathogenic risks is customized; wherein the second preset value is 4, and the copy number in the human genome is 4 copies at most.

(4) Deleting the columns with preset column names;

in an embodiment of the present invention, the preset column names include: columns of "CnvName", "start _ bin", "end _ bin", "cnv _ length", "continue _ bin _ num", "bin _ num", "raito", "z-score", "Tag", "cytoBand", "gene", "OMIM", "decipher", "DGV".

(5) Splitting the file according to chromosomes: for the matching R program, the repeated and missing variant types are split according to chromosome and named separately.

Specifically, the matching R program needs to split the repeated variant types by chromosome, named as "dup 1. txt", split the deletion variant types by chromosome, named as "indel 1. txt".

And step S2, automatically drawing the vector diagram and pdf diagram in the svg format.

In the embodiment of the present invention, R-program rendering may be employed.

Firstly, a plurality of chromosomes are arranged in groups, wherein the first group is chromosomes 1-3, the second group is chromosomes 4-5, the third group is chromosomes 6-12, the fourth group is chromosomes 13-15, the fifth group is chromosomes 16-18, the sixth group is chromosomes 19-20, the seventh group is chromosomes 21-22, and the eighth group is female X chromosome/male X-Y chromosome.

Then, carrying out equal scaling on the chromosome; according to the color and the serial number of the novel marking bands of the chromosome bands, marking the centromere locus of the chromosome according to the centromere position of the chromosome; drawing a scale on the right side of the chromosome, and substituting the data of the repeated mutation type and the missing mutation type into the map respectively to generate a vector map and a pdf map in a svg format.

The following describes a process for automatically drawing vector diagrams and pdf diagrams in svg format by using an R program according to a specific embodiment.

1. 24 chromosomes are arranged in groups, wherein the first group is chromosomes 1-3, the second group is chromosomes 4-5, the third group is chromosomes 6-12, the fourth group is chromosomes 13-15, the fifth group is chromosomes 16-18, the sixth group is chromosomes 19-20, the seventh group is chromosomes 21-22, and the eighth group is female X chromosome/male X-Y chromosome.

2. The 24 chromosomes were scaled equally according to the scale of a4 paper.

3. And marking the strip color and the strip number according to the chromosome strip information.

4. The centromere locus is labeled according to the chromosomal centromere position.

5. The chromosomes are scaled to the right with the labels "0", "1", "2", "3", "4", where "0" represents 0 copy number, "1" represents 1 copy number, "2" represents 2 copy numbers, "3" represents 3 copy numbers, and "4" represents 4 copy numbers. Female X chromosome markers "0", "1", "2", "3", "4"; the male X chromosome markers are "0", "1", "2", and the Y chromosome markers are "0", "1", "2".

6. Data for the repeat variant types are included in the figure, with the horizontal representing copy number size, the vertical representing the specific location of the repeat variant on the chromosome as CNV length, and the blue representing repeats (replication).

7. Data of the Deletion variant type are put into the graph, with horizontal representing the copy number size, vertical representing the specific position of the repeat variant on the chromosome as the CNV length, and red representing the Deletion (Deletion).

8. Wherein the male sex chromosome contains "X" and "Y" and has a copy number of 2 or less, and the female sex chromosome only contains "X" and has a copy number of 4 or less.

And generating a vector diagram and a pdf diagram with the file format of svg format. FIG. 3 is a vector diagram of the svg format of a male X-Y chromosome implemented using the mapping method of the present invention; fig. 4 is a vector diagram of the svg format of female X chromosome realized by the mapping method of the present invention.

Drawing 24 chromosomes from a male sample, comprising: 22 autosomes + X chromosome + Y chromosome;

drawing 23 chromosomes from the female sample, including: 22 autosomes + X chromosomes, female sample X chromosomes had no dup.

At present, reading personnel analyze clinical data according to CNV annotation files, tens of millions of rows of data need much time and energy, the position of the repeat and deletion variation of a large segment on a chromosome and the size of the repeat and deletion variation can be quickly found in a visualization graph mode, all the repeat and deletion variations can be clear at a glance, and the working efficiency is greatly improved.

As shown in fig. 2, an embodiment of the present invention further provides an automated data processing and mapping system, including: a data automation processing module 100 and an automation drawing module 200.

The data automated processing module 100 is configured to adopt a computer programming language to automatically process preset logic of data, and includes:

(1) and splitting data according to a preset CNV variation type.

In an embodiment of the present invention, the setting of the predetermined CNV variation type by the data automation processing module 100 includes: deletion variations and repeat variations. The computer programming language can adopt python program or c + + and other programming languages.

(2) Acquiring an annotation file, wherein target data to be processed are recorded in the annotation file, and the variation of the pathogenicity risk is customized for the absolute value of a normalized value z score (standard value z-score) z score of the target data in the annotation file, which is greater than a first preset value;

preferably, the first preset value is 3. It should be noted that the above values are only selected for the purpose of illustration, and are not intended to limit the present invention, and other values may be selected as needed.

(3) Obtaining an annotation file, wherein target data to be processed are recorded in the annotation file, and the copy number CopyNum of the target data in the annotation file is less than or equal to a second preset value, so that the variation of pathogenic risks is customized; wherein the second predetermined value is 4, and the copy number in the human genome is 4 copies at most

(4) The column of the preset column name is deleted.

In an embodiment of the present invention, the preset column names include: columns of "CnvName", "start _ bin", "end _ bin", "cnv _ length", "continue _ bin _ num", "bin _ num", "raito", "z-score", "Tag", "cytoBand", "gene", "OMIM", "decipher", "DGV".

(5) Splitting the file according to chromosomes: for the matching R program, the repeated and missing variant types are split according to chromosome and named separately.

Specifically, the data automation processing module 100 matches the R program and needs to split the repeated variant type by chromosome, named in the form of dup1.txt, and split the deletion variant type by chromosome, named in the form of indel1. txt.

The automatic drawing module 200 is used for automatically drawing the vector diagram and the pdf diagram in the svg format by using an R program. In the embodiment of the present invention, R-program rendering may be employed.

Specifically, the automatic mapping module 200 first places a plurality of chromosomes in groups, wherein the first group is chromosomes 1-3, the second group is chromosomes 4-5, the third group is chromosomes 6-12, the fourth group is chromosomes 13-15, the fifth group is chromosomes 16-18, the sixth group is chromosomes 19-20, the seventh group is chromosomes 21-22, and the eighth group is female X chromosome/male X-Y chromosome. Then, carrying out equal scaling on the chromosome; according to the color and the serial number of the novel marking bands of the chromosome bands, marking the centromere locus of the chromosome according to the centromere position of the chromosome; drawing a scale on the right side of the chromosome, and substituting the data of the repeated mutation type and the missing mutation type into the map respectively to generate a vector map and a pdf map in a svg format. Drawing 24 chromosomes from a male sample, comprising: 22 autosomes + X chromosome + Y chromosome;

drawing 23 chromosomes from the female sample, including: 22 autosomes + X chromosomes, female sample X chromosomes had no dup.

At present, reading personnel analyze clinical data according to CNV annotation files, tens of millions of rows of data need much time and energy, the position of the repeat and deletion variation of a large segment on a chromosome and the size of the repeat and deletion variation can be quickly found in a visualization graph mode, all the repeat and deletion variations can be clear at a glance, and the working efficiency is greatly improved.

The core of the method and the system for automatically processing data and drawing the graph is the automatic processing of the python program on the data and the automatic drawing of the vector diagram and the pdf diagram in the svg format by the R program. Specifically, by combining python program data processing and R program visual mapping, a clinical sample can be processed in a few minutes, the position of the repeat and deletion variation of a large segment on a chromosome and the size of the repeat and deletion variation can be quickly and accurately found, all the repeat and deletion variation can be clearly seen, the working efficiency is greatly improved, and the clinical interpretation can be better served. The software capable of rapidly processing data and drawing is developed based on Python and R, the filtering and splitting of clinical samples can be rapidly and accurately realized within 1 minute through the preset logic of the Python program, the efficiency is greatly improved, the vector diagram and the pdf diagram in the svg format can be automatically drawn within 2 minutes by bringing the data processed by the Python program into the R program, and the working efficiency of clinical unscrambler is greatly improved.

In the description herein, references to the description of the term "one embodiment," "some embodiments," "an example," "a specific example," or "some examples," etc., mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.

Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention, and that variations, modifications, substitutions and alterations can be made in the above embodiments by those of ordinary skill in the art without departing from the principle and spirit of the present invention. The scope of the invention is defined by the appended claims and equivalents thereof.