CN107808073A - High-flux microorganism functional gene microarray processing method and electronic equipment - Google Patents
High-flux microorganism functional gene microarray processing method and electronic equipment Download PDFInfo
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- CN107808073A CN107808073A CN201711046082.3A CN201711046082A CN107808073A CN 107808073 A CN107808073 A CN 107808073A CN 201711046082 A CN201711046082 A CN 201711046082A CN 107808073 A CN107808073 A CN 107808073A
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- G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16B25/00—ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
Abstract
The present invention, which discloses a kind of high-flux microorganism functional gene microarray processing method and electronic equipment, method, to be included：According to the number of selected function gene probe, selection includes the minimum default specification of the number of selected function gene probe as current specifications, obtain the signal value of multiple probes in the microarray of current specifications, the microarray is divided into multiple subarrays, the probe of each subarray includes gene probe and polytype control probe, and the control probe comprises at least：Background value control probe, positive control probe, negative control probe and global control probe；Background value processing, Denoising disposal and standardization are carried out to acquired signal value.The present invention can build microarray automatically and carry out Signal Pretreatment, so as to successfully manage due to the interference of various environmental factors and manual operation suffered by high flux microarray hybridization experiment in reality, and the signal value of covered objective function gene is obtained as precisely as possible.
Description
Technical field
The present invention relates to environmental microorganism metagenomics and bioinformatics research field, particularly a kind of high flux is micro-
Biological function gene microarray processing method and electronic equipment.
Background technology
High-flux microorganism functional gene microarray is widely used in analyzing complicated microbiologic population, and numerous studies put into practice exhibition
Show that it is quantifying to detect microbial function composition, structure and contacts each side at diversity between external environmental factor
It is high-effect.With molecular biology, the fast development of genomics, bioinformatics, microbial function gene microarray
Flux more and more higher, at the same remain its detect it is high special possessed by microbial function, it is high sensitive, high quantization and high repeat
Characteristic, it is contemplated that will persistently be played an important role in the research practice of solution analyzing soil microbial community.
High-flux microorganism functional gene microarray is needed tens of thousands of hundreds of thousands individual functional probe arrangements even up to a million
On one piece of small-sized matrix slide, due in reality the experiment of high flux microarray hybridization unavoidably can by various environmental factors and
The interference of manual operation, the structure of microarray can not be only that the probe random distribution elected is formed microarray, and need
Abnormal conditions as more as possible are considered to ensure that hybrid experiment data are as accurate as possible and are easy to handle.Otherwise, some are small
Abnormal conditions (such as experiment hybrid dna inequality) may cause subsequent treatment and analyze hard to carry on.
Firstly, since original microarray hybridization results can not generally avoid substantial amounts of noise signal, therefore the structure of microarray
Build and have to consider how to set negative positive and global control probe effectively to distinguish actual signal and noise signal
Come.Meanwhile the result of single microarray hybridization is likely to be influenceed by ambient impurities, so as to produce different value signal (this
A little signals are typically saturated uneven).Therefore how effectively the structure of array must account for differentiates and to remove these different
Value signal.Furthermore the layout of structure especially its probe of microarray has to consider that recurrent hybridization is not in experiment
Uniform situation, including different microarrays may be overall higher or relatively low, and part is higher or relatively low in same microarray.Battle array
The mode of the structure of row allows for being advantageous to carry out the signal value standardization inside microarray and between microarray.Reality
Be so it is complicated and changeable so that micro-array construction in itself be challenge it is heavy, and further to formulate a set of flow will be whole
It is even more extremely difficult, it is necessary to largely test and calculate that individual building process standardization and automation take into account subsequent result analysis simultaneously
The experience of aspect could be carried out effectively.
The content of the invention
Based on this, it is necessary to test easily suffered various environmental factors for the high flux microarray hybridization of prior art
And the technical problem of the interference of manual operation, there is provided a kind of high-flux microorganism functional gene microarray processing method and electronics
Equipment.
The present invention provides a kind of high-flux microorganism functional gene microarray processing method, including：
According to the number of selected function gene probe, selection includes the minimum of the number of selected function gene probe and preset
Specification obtains the signal value of multiple probes in the microarray of current specifications, the microarray is divided into multiple as current specifications
Subarray, the probe of each subarray include gene probe and polytype control probe, and the control probe at least wraps
Include：Background value control probe, positive control probe, negative control probe and global control probe；
Background value processing, Denoising disposal and standardization are carried out to acquired signal value.
Further, the control probe for each subarray, is planned in the following way：
The multiple background value control probes of random distribution；
The multiple negative control probes of random distribution；
In the multiple positive control probes of the start of line of subarray first and the distribution of footline end；
In subarray center radial probes are controlled to the multiple overall situations of corner diffusion profile.
Further, it is described to go background value to handle, specifically include：
To each subarray：
The signal value average of all background value control probes in the subarray is calculated, the background value is controlled into probe
Background value of the signal value average as the subarray；
Background value of subarray, obtains each probe where the probe signals value of each probe in the subarray is subtracted into it
True signal value.
Further, the Denoising disposal, is specifically included：
The signal of each probe is calculated than level of noise and value for coefficient of variation；
Calculate the signal value average of all interior negative control probes of each subarray；
Value for coefficient of variation in each subarray is marked as different value signal more than the probe of default outlier threshold and removed；
It is more than for each subarray setting signal than noise threshold, the signal than noise threshold 95% in the subarray
Signal is marked as making an uproar by the signal of feminine gender control probe less than the signal than level of noise than level of noise than the probe of noise threshold
Acoustical signal simultaneously removes.
Further, the standardization, is specifically included：
The signal value average of all calibrated probes in each subarray is calculated, the calibrated probe is the positive
Control probe and/or the global control probe；
The signal value average of calibrated probe maximum in all subarrays is selected as standardization average；
For each subarray, the standardization average divided by the signal value average of the calibrated probe of the subarray are made
For the normalization factor of the subarray；
The signal value of probe in the subarray in addition to calibrated probe is multiplied by the normalization factor and obtains standard
Probe signals value after change.
The present invention provides a kind of electronic equipment, including：
At least one processor；And
The memory being connected with least one processor communication；Wherein,
The memory storage has can be by the instruction of one computing device, and the instruction is by least one place
Manage device to perform, so that at least one processor can：
According to the number of selected function gene probe, selection includes the minimum of the number of selected function gene probe and preset
Specification obtains the signal value of multiple probes in the microarray of current specifications, the microarray is divided into multiple as current specifications
Subarray, the probe of each subarray include gene probe and polytype control probe, and the control probe at least wraps
Include：Background value control probe, positive control probe, negative control probe and global control probe；
Background value processing, Denoising disposal and standardization are carried out to acquired signal value.
Further, the control probe for each subarray, is planned in the following way：
The multiple background value control probes of random distribution；
The multiple negative control probes of random distribution；
In the multiple positive control probes of the start of line of subarray first and the distribution of footline end；
In subarray center radial probes are controlled to the multiple overall situations of corner diffusion profile.
Further, it is described to go background value to handle, specifically include：
To each subarray：
The signal value average of all background value control probes in the subarray is calculated, the background value is controlled into probe
Background value of the signal value average as the subarray；
Background value of subarray, obtains each probe where the probe signals value of each probe in the subarray is subtracted into it
True signal value.
Further, the Denoising disposal, is specifically included：
The signal of each probe is calculated than level of noise and value for coefficient of variation；
Calculate the signal value average of all interior negative control probes of each subarray；
Value for coefficient of variation in each subarray is marked as different value signal more than the probe of default outlier threshold and removed；
It is more than for each subarray setting signal than noise threshold, the signal than noise threshold 95% in the subarray
Signal is marked as making an uproar by the signal of feminine gender control probe less than the signal than level of noise than level of noise than the probe of noise threshold
Acoustical signal simultaneously removes.
Further, the standardization, is specifically included：
The signal value average of all calibrated probes in each subarray is calculated, the calibrated probe is the positive
Control probe and/or the global control probe；
The signal value average of calibrated probe maximum in all subarrays is selected as standardization average；
For each subarray, the standardization average divided by the signal value average of the calibrated probe of the subarray are made
For the normalization factor of the subarray；
The signal value of probe in the subarray in addition to calibrated probe is multiplied by the normalization factor and obtains standard
Probe signals value after change.
The present invention can build microarray automatically and carry out Signal Pretreatment, so as to successfully manage due to high flux in reality
The interference of various environmental factors and manual operation suffered by microarray hybridization experiment, and obtain covered as precisely as possible
Objective function gene signal value.
Brief description of the drawings
Fig. 1 is a kind of high-flux microorganism functional gene microarray processing method of the present invention；
Fig. 2 is the hardware architecture diagram of a kind of electronic equipment of the present invention.
Embodiment
The present invention will be further described in detail with specific embodiment below in conjunction with the accompanying drawings.
It is as shown in Figure 1 a kind of high-flux microorganism functional gene microarray processing method of the present invention, including：
Step S101, according to the number of selected function gene probe, selection includes the number of selected function gene probe
Minimum default specification obtains the signal value of multiple probes in the microarray of current specifications, the microarray as current specifications
Multiple subarrays are divided into, the probe of each subarray includes gene probe and polytype control probe, the control
Probe comprises at least：Background value control probe, positive control probe, negative control probe and global control probe；
Step S102, background value processing, Denoising disposal and standardization are carried out to acquired signal value.
Specifically, the present invention presets four kinds of specifications, can accommodate altogether about 60,000,180,000,400,000 and 100 respectively
Ten thousand DNA probes.Most covering comprehensive microbial function gene microarray in the world about includes 160,000 functional genes at present
Probe, therefore the default specification of the present embodiment can be in a very long time in future still meet demand.Then, according to selected work(
The number of energy gene probe, the present embodiment will select default specification automatically as micro-array construction carrier.It is if for example, constructed
Microarray need to include the probe of 50,000 or so, then 60,000 default specifications will be chosen automatically；If array needs to include
100000 probes, then 180,000 default specifications will be selected.And then, for the microarray of each different size, journey
Automatic virtualization is partitioned into the subarray of varying number, containing about 250 probes of each subarray by sequence.So 60,000 default specifications
240 subarrays will be included altogether, 180,000 default specifications will include 720 subarrays altogether, and 400,000 default specifications will be total
Include 1600 subarrays altogether, 1,000,000 default specifications will include 4000 subarrays altogether.
Background value control probe uses the negative control probes of Agilent；Feminine gender control probe is derived from eight unusual rings
Very rare thermophilic bacteria strain in border；Positive control probe uses 16S conservative regions；Overall situation control probe is then COR
Universal probes.
The present invention can build microarray automatically and carry out Signal Pretreatment, so as to successfully manage due to high flux in reality
The interference of various environmental factors and manual operation suffered by microarray hybridization experiment, and obtain covered as precisely as possible
Objective function gene signal value.
In one of the embodiments, the control probe for each subarray, is planned in the following way：
The multiple background value control probes of random distribution；
The multiple negative control probes of random distribution；
In the multiple positive control probes of the start of line of subarray first and the distribution of footline end；
In subarray center radial probes are controlled to the multiple overall situations of corner diffusion profile.
Specifically, in each subarray, in addition to functional gene probe, automatic planning is made it to comprise at least by program
Four kinds of different control probes, including background value control probe, positive control probe, feminine gender control probe and global control are visited
Pin.Wherein background value control probe (2 to 3) and negative control probe (8 to 10) random distribution, positive control probe (16
It is individual) be located at the start of line of subarray first (8) and footline end (8), overall situation control probe (5) positioned at subarray center into
It is radial to be spread to corner.
The present embodiment has used the division of subarray, processing mode at least two benefits of this refinement.It is first, every
Every signal value processing of one probe can be carried out based on the control probe in subarray, because miscellaneous suffered by closely located probe
The actual conditions influence of friendship is relatively similar, so it is possible to prevente effectively from the signal value of probe is handled by the control probe of hypertelorism
Influence, so as to improve the accuracy of pretreatment.Second, it is possible that local higher or inclined in same microarray in crossover process
Low situation, and by dividing subarray and setting control pointer can be extremely effective in the identical relative position of each subarray
Ground standardizes the signal value in same microarray, and the standardization of signal value provides a more accurately basis between microarray.
In one of the embodiments, it is described to go background value to handle, specifically include：
To each subarray：
The signal value average of all background value control probes in the subarray is calculated, the background value is controlled into probe
Background value of the signal value average as the subarray；
Background value of subarray, obtains each probe where the probe signals value of each probe in the subarray is subtracted into it
True signal value.
The present embodiment is the calculating of the true signal value of single subarray background value and probe.The present invention is in each submatrix
In row, the signal value average of background value control probe is calculated, and using the signal value average as each spy in the subarray
The background value of pin.Then, the Part Methods will calculate the true signal value of each probe, and calculation is the probe signals
The background value of subarray where value subtracts it.
The present embodiment employs the special environment value and controls probe as static background value, so as to be advantageous to calculate each spy
The true signal value of pin, it is not easily susceptible to the influence of sample DNA concentration difference.
In one of the embodiments, the Denoising disposal, is specifically included：
The signal of each probe is calculated than level of noise and value for coefficient of variation；
Calculate the signal value average of all interior negative control probes of each subarray；
Value for coefficient of variation in each subarray is marked as different value signal more than the probe of default outlier threshold and removed；
Signal in each subarray is marked as noise signal less than preset signals than level of noise than the probe of noise threshold
And remove or negative control probe to have normal signal be the automatic setting signal of standard than level of noise threshold must not exceed 10%
Value.
The present embodiment is the different value processing of Microarray signals and denoising.Specifically, the signal of each probe is calculated
Than level of noise and value for coefficient of variation, and feminine gender controls the average of probe in each subarray, and whole array signal is entered
The different value processing of row and denoising.Different value processing is based primarily upon value for coefficient of variation, if the value for coefficient of variation of some probe exceedes
0.8, then it will be marked as different value signal and be removed.Denoising is more negative than in level of noise and subarray by basis signal
The average combination of probe is controlled to carry out.The present invention can both set a default experience signal than noise threshold (generally 2) with
All probes less than the threshold value are marked as noise signal and are removed, can also must not exceed 5% negative control probe has normally
Signal is that the next automatic setting signal of standard compares noise threshold.
The present embodiment controls probe by calculating probe signals than level of noise and value for coefficient of variation, and using negative, should
Method not only can effectively remove different value signal and effectively actual signal and microarray hybridization experiment can not generally can also be kept away
Exempt from substantial amounts of noise signal to make a distinction.
In one of the embodiments, the standardization, is specifically included：
The signal value average of all calibrated probes in each subarray is calculated, the calibrated probe is the positive
Control probe and/or the global control probe；
The signal value average of calibrated probe maximum in all subarrays is selected as standardization average；
For each subarray, the standardization average divided by the signal value average of the calibrated probe of the subarray are made
For the normalization factor of the subarray；
The signal value of probe in the subarray in addition to calibrated probe is multiplied by the normalization factor and obtains standard
Probe signals value after change.
The present embodiment is that signal value standardizes between the standardization of overall signal value and microarray inside microarray.Calculate each
The positive average for controlling probe and global control probe in subarray, so as between microarray inside overall signal value and microarray
Signal value standardization not only can be based on the former average but also can be based on the latter or the combination of the two.It is comprised the following steps that：It is first
Positive control probe or global control probe average highest one are first found from all subarrays.Then, calculate each
Normalization factor corresponding to individual subarray, computational methods be with the positive control probe of highest or global control probe average divided by
The positive control probe of this subarray or global control probe average.Then, the standardization drawn by being multiplied by previous step
The factor is with the overall signal value for lifting each subarray.Finally, if handling multiple microarrays simultaneously, this method will be entered automatically
Signal value standardizes between row microarray, and its specific method and phase on the methodological principle of microarray inside overall signal value standardization
Together.During implementation, each microarray is by the subarray in corresponding microarray internal normalization, and the positive in each microarray
The average of control probe and global control probe will act as the key value of signal value standardization.
The present embodiment is worked along both lines using positive control probe and global control probe, so as to frequent in micro- experiment
The uneven situation of the microarray hybridization of generation is normalized into same level and is compared so that analysis result is more accurate.
The hardware architecture diagram of a kind of electronic equipment of the present invention is illustrated in figure 2, including：
At least one processor 201；And
The memory 202 communicated to connect with least one processor 201；Wherein,
The memory 202 is stored with can be by the instruction of one computing device, and the instruction is by described at least one
Individual processor 201 performs, so that at least one processor 201 can：
According to the number of selected function gene probe, selection includes the minimum of the number of selected function gene probe and preset
Specification obtains the signal value of multiple probes in the microarray of current specifications, the microarray is divided into multiple as current specifications
Subarray, the probe of each subarray include gene probe and polytype control probe, and the control probe at least wraps
Include：Background value control probe, positive control probe, negative control probe and global control probe；
Background value processing, Denoising disposal and standardization are carried out to acquired signal value.
In Fig. 2 by taking a processor 202 as an example.
Server can also include：Input unit 203 and output device 204.
Processor 201, memory 202, input unit 203 and display device 204 can pass through bus or other modes
Connect, in figure exemplified by being connected by bus.
Memory 202 is used as a kind of non-volatile computer readable storage medium storing program for executing, available for storage non-volatile software journey
Sequence, non-volatile computer executable program and module, as the high-flux microorganism functional gene in the embodiment of the present application is micro-
Programmed instruction/module corresponding to array processing method, for example, the method flow shown in Fig. 1.Processor 201 is stored by running
Non-volatile software program, instruction and module in memory 202, so as to perform at various function application and data
Reason, that is, realize the high-flux microorganism functional gene microarray processing method in above-described embodiment.
Memory 202 can include storing program area and storage data field, wherein, storing program area can store operation system
Application program required for system, at least one function；Storage data field can be stored according to the micro- battle array of high-flux microorganism functional gene
Column processing method uses created data etc..In addition, memory 202 can include high-speed random access memory, may be used also
With including nonvolatile memory, a for example, at least disk memory, flush memory device or the storage of other nonvolatile solid states
Device.In certain embodiments, memory 202 is optional including relative to the remotely located memory of processor 201, these are long-range
Memory can pass through network connection to the device for performing high-flux microorganism functional gene microarray processing method.Above-mentioned network
Example include but is not limited to internet, intranet, LAN, mobile radio communication and combinations thereof.
The user that input unit 203 can receive input clicks on, and produces and high-flux microorganism functional gene microarray
The signal input that the user of processing method is set and function control is relevant.Display device 204 may include that the displays such as display screen are set
It is standby.
It is stored in one or more of modules in the memory 202, when by one or more of processing
When device 201 is run, the high-flux microorganism functional gene microarray processing method in above-mentioned any means embodiment is performed.
In one of the embodiments, the control probe for each subarray, is planned in the following way：
The multiple background value control probes of random distribution；
The multiple negative control probes of random distribution；
In the multiple positive control probes of the start of line of subarray first and the distribution of footline end；
In subarray center radial probes are controlled to the multiple overall situations of corner diffusion profile.
In one of the embodiments, it is described to go background value to handle, specifically include：
To each subarray：
The signal value average of all background value control probes in the subarray is calculated, the background value is controlled into probe
Background value of the signal value average as the subarray；
Background value of subarray, obtains each probe where the probe signals value of each probe in the subarray is subtracted into it
True signal value.
In one of the embodiments, the Denoising disposal, is specifically included：
The signal of each probe is calculated than level of noise and value for coefficient of variation；
Calculate the signal value average of all interior negative control probes of each subarray；
Value for coefficient of variation in each subarray is marked as different value signal more than the probe of default outlier threshold and removed；
It is more than for each subarray setting signal than noise threshold, the signal than noise threshold 95% in the subarray
Signal is marked as making an uproar by the signal of feminine gender control probe less than the signal than level of noise than level of noise than the probe of noise threshold
Acoustical signal simultaneously removes.
In one of the embodiments, the standardization, is specifically included：
The signal value average of all calibrated probes in each subarray is calculated, the calibrated probe is the positive
Control probe and/or the global control probe；
The signal value average of calibrated probe maximum in all subarrays is selected as standardization average；
For each subarray, the standardization average divided by the signal value average of the calibrated probe of the subarray are made
For the normalization factor of the subarray；
The signal value of probe in the subarray in addition to calibrated probe is multiplied by the normalization factor and obtains standard
Probe signals value after change.
Embodiment described above only expresses the several embodiments of the present invention, and its description is more specific and detailed, but simultaneously
Therefore the limitation to the scope of the claims of the present invention can not be interpreted as.It should be pointed out that for one of ordinary skill in the art
For, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to the guarantor of the present invention
Protect scope.Therefore, the protection domain of patent of the present invention should be determined by the appended claims.
Claims (10)
- A kind of 1. high-flux microorganism functional gene microarray processing method, it is characterised in that including：According to the number of selected function gene probe, selection includes the minimum default specification of the number of selected function gene probe As current specifications, the signal value of multiple probes in the microarray of current specifications is obtained, the microarray is divided into multiple submatrixs Row, the probe of each subarray include gene probe and polytype control probe, and the control probe comprises at least： Background value control probe, positive control probe, negative control probe and global control probe；Background value processing, Denoising disposal and standardization are carried out to acquired signal value.
- 2. high-flux microorganism functional gene microarray processing method according to claim 1, it is characterised in that for every The control probe of individual subarray, is planned in the following way：The multiple background value control probes of random distribution；The multiple negative control probes of random distribution；In the multiple positive control probes of the start of line of subarray first and the distribution of footline end；In subarray center radial probes are controlled to the multiple overall situations of corner diffusion profile.
- 3. high-flux microorganism functional gene microarray processing method according to claim 1, it is characterised in that described to go Background value processing, is specifically included：To each subarray：The signal value average of all background value control probes in the subarray is calculated, the background value is controlled to the letter of probe Number background value of the value average as the subarray；Background value of subarray, obtains the true of each probe where the probe signals value of each probe in the subarray is subtracted into it Real signal value.
- 4. high-flux microorganism functional gene microarray processing method according to claim 1, it is characterised in that described to go Noise processed, specifically include：The signal of each probe is calculated than level of noise and value for coefficient of variation；Calculate the signal value average of all interior negative control probes of each subarray；Value for coefficient of variation in each subarray is marked as different value signal more than the probe of default outlier threshold and removed；It is more than in the subarray 95% feminine gender than noise threshold than noise threshold, the signal for each subarray setting signal Control the signal of probe that signal is marked as into noise letter than the probe of noise threshold less than the signal than level of noise than level of noise Number and remove.
- 5. high-flux microorganism functional gene microarray processing method according to claim 1, it is characterised in that the mark Quasi-ization processing, is specifically included：The signal value average of all calibrated probes in each subarray is calculated, the calibrated probe is the positive control Probe and/or the global control probe；The signal value average of calibrated probe maximum in all subarrays is selected as standardization average；For each subarray, the standardization average divided by the signal value average of the calibrated probe of the subarray are regard as this The normalization factor of subarray；The signal value of probe in the subarray in addition to calibrated probe is multiplied by after the normalization factor obtains standardization Probe signals value.
- 6. a kind of electronic equipment, it is characterised in that including：At least one processor；AndThe memory being connected with least one processor communication；Wherein,The memory storage has can be by the instruction of one computing device, and the instruction is by least one processor Perform, so that at least one processor can：According to the number of selected function gene probe, selection includes the minimum default specification of the number of selected function gene probe As current specifications, the signal value of multiple probes in the microarray of current specifications is obtained, the microarray is divided into multiple submatrixs Row, the probe of each subarray include gene probe and polytype control probe, and the control probe comprises at least： Background value control probe, positive control probe, negative control probe and global control probe；Background value processing, Denoising disposal and standardization are carried out to acquired signal value.
- 7. electronic equipment according to claim 6, it is characterised in that the control probe for each subarray, using such as Under type is planned：The multiple background value control probes of random distribution；The multiple negative control probes of random distribution；In the multiple positive control probes of the start of line of subarray first and the distribution of footline end；In subarray center radial probes are controlled to the multiple overall situations of corner diffusion profile.
- 8. electronic equipment according to claim 6, it is characterised in that it is described to go background value to handle, specifically include：To each subarray：The signal value average of all background value control probes in the subarray is calculated, the background value is controlled to the letter of probe Number background value of the value average as the subarray；Background value of subarray, obtains the true of each probe where the probe signals value of each probe in the subarray is subtracted into it Real signal value.
- 9. electronic equipment according to claim 6, it is characterised in that Denoising disposal, specifically include：The signal of each probe is calculated than level of noise and value for coefficient of variation；Calculate the signal value average of all interior negative control probes of each subarray；Value for coefficient of variation in each subarray is marked as different value signal more than the probe of default outlier threshold and removed；It is more than in the subarray 95% feminine gender than noise threshold than noise threshold, the signal for each subarray setting signal Control the signal of probe that signal is marked as into noise letter than the probe of noise threshold less than the signal than level of noise than level of noise Number and remove.
- 10. electronic equipment according to claim 6, it is characterised in that the standardization, specifically include：The signal value average of all calibrated probes in each subarray is calculated, the calibrated probe is the positive control Probe and/or the global control probe；The signal value average of calibrated probe maximum in all subarrays is selected as standardization average；For each subarray, the standardization average divided by the signal value average of the calibrated probe of the subarray are regard as this The normalization factor of subarray；The signal value of probe in the subarray in addition to calibrated probe is multiplied by after the normalization factor obtains standardization Probe signals value.
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| CN101935699A (en) * | 2009-06-30 | 2011-01-05 | 希森美康株式会社 | Methods for detecting nucleic acid with microarray and microarray data analysis apparatus |
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| CN1606695A (en) * | 2001-12-21 | 2005-04-13 | 阿菲梅特里克斯公司 | High throughput resequencing and variation detection using high density microarrays |
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| WO2004044700A2 (en) * | 2002-11-12 | 2004-05-27 | Affymetrix, Inc. | Methods, compositions and computer software products for interrogating sequence variations in functional genomic regions |
| WO2005001123A1 (en) * | 2003-06-30 | 2005-01-06 | Tsinghua University | Dna chip based genetic typing |
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| CN101206216A (en) * | 2006-12-20 | 2008-06-25 | 三星电子株式会社 | Oligomer probe array chip, related mask and analysis method |
| CN101935699A (en) * | 2009-06-30 | 2011-01-05 | 希森美康株式会社 | Methods for detecting nucleic acid with microarray and microarray data analysis apparatus |
| CN102534013A (en) * | 2012-01-18 | 2012-07-04 | 李越希 | Gene chip for high-flux detection of pathogens and application thereof |
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