METHOD AND APPARATUS FOR INTRA- AND INTER-PLATFORM INFORMATION TRANSFORMATION AND REUSE IN PREDICTIVE ANALYTICS AND PATTERN RECOGNITION

A method and a system for interpreting data between two quantitative genomic datasets are described, wherein datasets are associated with the same disease or condition, for example, samples from the same patient obtained on different genomic platforms with varying data acquisition parameters. The data samples in each of the first and second datasets are rank ordered and the relative distances among the data samples are determined. The value ranks and relative distances are then used to correlate to data samples in the first and second quantitative genomic datasets, with the output provided to a user, such as a clinician or a patient.

FIELD

The present disclosure generally relates to method and systems for inter- and intra-platform data transformation and reuse in predictive analysis, particularly, in genomics. More specifically, the present disclosure relates to translation and reuse of information obtained from one gene expression dataset, obtained using a first gene expression generation platform, for interpretation of another gene expression dataset, obtained using that platform and/or another genomic data generation platform.

BACKGROUND

Important biological studies for biomarkers are often tied to existing prevalent genomic data generation platforms. Meanwhile, the performance levels offered by existing prevalent platforms are often quickly surpassed by newly developed genomic data generation platforms, leading researchers, practitioners, or those involved in biological studies to switch to using newer platforms in their studies. However, while the newer genomic data generation platforms are often more accurate and/or more sensitive than previously existing platforms, these newer platforms can vary from previously existing platforms in their dynamic range. Biological variations and technical variations (e.g., variations introduced by technicians or variations introduced by slight protocol changes) can also be present among the datasets obtained from various platforms. Due to these differences, data obtained from one genomic data generation platform cannot always be readily interpreted or used by another genomic data generation platform. Thus, there exists a need for mapping measurements of an existing technological platform to a new and often many times more accurate or sensitive platform. There is a similar problem in biomedical imaging as newer technologies provide an ever-increasing resolution.

SUMMARY

In one aspect, a method for interpreting data between two quantitative genomic datasets, obtained on different genomic platforms is featured. The datasets are associated with a same disease or condition, and each dataset comprises a plurality of genomic data sample values optionally associated with labels. The featured method includes:

a) accepting a first dataset, comprising data values A and pre-assigned labels A if available, or creating associated labels A and thereupon assigning labels A to values A;

b) accepting a second dataset comprising data values B;

c) computing associated value rank and relative distances for each value A in the first dataset and for each value B in the second dataset; and

d) correlating at least one value A to at least one value B based on the parameters computed in step c); and

e) assigning label(s) B to the values B correlated to values A, wherein each label B has a corresponding matching label A assigned to value A, thereby producing a correlated data set B, comprising values B and associated labels B.

In yet another aspect, a computer program product is described. The computer program product is tangibly embodied in a non-transitory computer readable storage medium that comprises instructions being operable to cause a data processing system to

a) accept a first dataset, comprising data values A and pre-assigned labels A if available, or creating associated labels A and thereupon assigning labels A to values A;

b) accept a second dataset comprising data values B;

c) compute associated value rank and relative distances for each value A in the first dataset and for each value B in the second dataset; and

d) correlate at least one value A to at least one value B based on the parameters computed in step c); and

e) assign label(s) B to the values B correlated to values A, wherein each label B has a corresponding matching label A assigned to value A, thereby producing a correlated data set B, comprising values B and associated labels B.

In other examples, any of the above aspects, or any system, method, apparatus, and computer program product method described herein, can include one or more of the following features.

The at least one value A can be correlated to the at least one value B using a predictive model, the predictive model including a training model that admits at least one of the ranks, relative distances, and labels assigned to the values A as training data. The training model can include at least one of regression analysis, Random Forest, or a machine learning technique.

The label(s) can indicate(s) at least one of presence or absence of information pertaining to the specific disease or disorder.

In an event the pre-assigned labels A are not available, one or more clusters of values A having one or more similar properties can be identified. The one or more clusters of values A can be identified by identifying two or more values in the values A having least one of same rank and relative distance values, similar rank and relative distance values, evenly distributed rank and relative distance values, or near-evenly distributed rank and relative distance values. The one or more clusters of values in the values B that correlate to the values included in the one or more clusters identified in the values A can be identified.

At least one of the values A or the values B can be obtained using at least one of Reverse Transcription-Polymerase Chain Reaction (RT-PCR), microarray sequencing, Bead Array microarray technology, proteomics, or a Next Generation Sequencing technique. At least one value from the values A can generated using a platform different from platform used to generate remaining values A.

The relative distances among the values can be obtained by determining a Rank-Specific Percentage of Sample Range (RSPSR) for each value, the RSPSR being a relative distance of the value normalized by sample value range in a sequence of ranked feature values. The dataset A can be obtained from a collection of datasets stored in a database that stores quantitative gene expression data obtained from at least one genomic data generation platform. The values A can be obtained from a database that stores quantitative gene expression data obtained from at least one genomic data generation platform. The values A and values B can be obtained from same subject or patient using the different genomic platforms.

At least one of the different data platforms can offer data acquisition properties not offered by other platforms. The data acquisition properties can include data resolution.

The interpretations obtained from interpreting the values B can be reported to a user. The user can be at least one of a physician, a clinician making a clinical determination, or a patient. The interpretations can include at least one of presence, level of expression, or absence of a gene, presence, level of expression, or absence of a gene signature, presence, level of expression, or absence of genetic material signaling propensity for developing the specific disease or disorder.

A patient's probability of developing the specific disease or disorder can be determined based on the interpretations and reporting the probability to the user. The patient can be assigned to a risk group based on the patient's probability of developing the specific disease or condition.

Other aspects and advantages of the invention can become apparent from the following drawings and description, all of which illustrate the principles of the invention, by way of example only.

DETAILED DESCRIPTION

Biological discoveries are often tied to specific platforms on which the discoveries are made. For example, genomic data can be generated on conceptually and technically different platforms, such as Reverse Transcription-Polymerase Chain Reaction (RT-PCR), microarray sequencing, Bead Array microarray technology, proteomics, and next generation sequencing techniques (e.g., RNA-Seq or RNA sequencing). These platforms often yield massive quantities of genomic data carrying valuable clinical information. However, due to the large quantity of data produced, the clinical information carried in the data can often only be extracted after computationally intensive processing, analysis, and validation. Once extracted, the clinical information is often tied to the platform from which it was obtained and cannot be easily used to interpret data obtained from other platform.

In the fast-paced field of genomics, new technologies tend to quickly surpass the performance of existing prevalent technologies. For example, as new DNA-genomic data generation platforms (e.g., next generation sequencing techniques) are introduced, older, more computationally intensive, less effective, or less efficient platforms are replaced with the newer platforms. The data generated, analyzed, and validated using these older platforms cannot, however, always be very easily interpreted and used by the newer platforms.

Similar issues may arise in the field of biomedical imaging. For example, newer imaging technologies may yield images having higher resolutions and, as such, be more desirable in conducting imaging studies. These imaging technologies, however, may not be readily capable of using information obtained from previously available technologies (e.g., technologies having lower imaging resolution capabilities) to interpret and understand the high resolution images that they generate. This inability to use previously obtained information is undesirable because it prevents the newer technologies from using information that has been already obtained from the previous technologies.

If the data and information obtained from the previous technologies is transformed or aligned, the newer technologies can leverage vast volume of information to increase their interpretation and analysis power to a great extent. For example, the newer technologies can use the already available information as a priori information in statistical analysis of the newly obtained data and/or reuse the already available information in predictive modeling.

The efficient data transformation described herein transforms data and information obtained from previously available and/or currently existing platforms into information that can be used by newer technologies to understand, interpret, analyze, and translate data obtained from the new technologies. As noted above, although the newer technologies are often more accurate or more sensitive than the previously existing platforms, they can still utilize data and information obtained from the previously existing platform to increase their efficiency and accuracy.

Further, although described in the context of genomics and gene expression data processing, biomedical imaging and molecular pathology and diagnostics, the embodiments disclosed herein are not limited to these areas and can be used in conjunction with other, similar, data acquisition technologies and platforms. For example, the embodiments described herein can be used to translate, interpret, or use information contained in images obtained using one imaging platform (e.g., a medical imaging platform, such as X-Ray) to understand images obtained from that platform or other independent platforms (e.g., another platform, such as a Medical Resonance Imaging (MRI) platform).

FIG. 1is a high-level block diagram of a data transformation and reuse system100according to an embodiment described herein. In the example shown inFIG. 1, the data transformation and reuse system100is shown as having been implemented in an interactive user device101(e.g., computer). However, the system100can be a computer implemented system and/or be implemented in digital electronic circuitry or computer hardware.

The user device101can be any device that includes a processor capable of carrying and/or implementing the procedures described herein. For example, the user device101can be a wireless phone, a smart phone, a personal digital assistant, a desktop computer, a laptop computer, a tablet computer, a handheld computer, a workstations, etc. Further, as noted above, one skilled in the art should appreciate that the system100can be implemented using any techniques known in the art, for example on an electronic chip.

In the example shown inFIG. 1, the user device that implements the system100includes a main memory130having an operating system133. The main memory130and the operating system133can be configured to implement various operating system functions. For example, the operating system133can be responsible for controlling access to various devices, implementing various functions of the user device101, and/or memory management. The main memory130can be any form of non-volatile memory included in machine-readable storage devices suitable for embodying data and computer program instructions. For example, the main memory130can be magnetic disk (e.g., internal or removable disks), magneto-optical disks, one or more of a semiconductor memory device (e.g., EPROM or EEPROM), flash memory, CD-ROM, and/or DVD-ROM disks.

The main memory133can also hold application software135. For example, the main memory130and application software135can include various computer executable instructions, application software, and data structures such as computer executable instructions and data structures that implement various aspects of the embodiments described herein. For example, the application software135can include various computer executable instructions, application software, and data structures such as computer executable instructions and data structures that implement the platform data converter137described herein.

The main memory130can also be connected to a cache unit (not shown) configured to store copies of the data from the most frequently used main memory120. The program codes that can be used with the embodiments disclosed herein can be implemented and written in any form of programming language, including compiled or interpreted languages, and can be deployed in any form, including as a stand-alone program or as a component, module, subroutine, or other unit suitable for use in a computing environment. A computer program can be configured to be executed on a computer, or on multiple computers, at one site or distributed across multiple sites and interconnected by a communications network160.

The networks160can have various topologies (e.g., bus, star, or ring network topologies) and/or be a private network (e.g., local area network (LAN)), a metropolitan area network (MAN), a wide area network (WAN), or a public network (e.g., the Internet). The network160can be a hybrid communications network160that includes all or parts of other networks.

Further, as noted above, the techniques described herein, without limitation, can be implemented in digital electronic circuitry or in computer hardware that executes software, firmware, or combinations thereof. The implementation can be as a computer program product, for example a computer program tangibly embodied in a non-transitory machine-readable storage device, for execution by, or to control the operation of, data processing apparatus, for example a computer, a programmable processor, or multiple computers.

One or more programmable processors can execute a computer program to operate on input data, perform function and methods described herein, and/or generate output data. An apparatus can be implemented as, and method steps can also be performed by, special purpose logic circuitry, such as a field programmable gate array (FPGA) or an application specific integrated circuit (ASIC). Components can refer to portions of the computer program and/or the processor or special circuitry that implements that functionality.

The user device101can also include a processor110that implements the various functions and methods described herein. The processor110can be connected to the main memory130. The processor110and the main memory130can be included in or supplemented by special purpose logic circuitry.

The processor110can include a central processing unit (CPU)115that includes processing circuitry configured to manipulate data structures from the main memory130and execute various instructions. For example, the processor110can be a general and/or special purpose microprocessor and any one or more processors of any kind of digital computer. Generally, the processor110can be configured to receive instructions and data from the main memory130(e.g., a read-only memory or a random access memory or both) and execute the instructions. The instructions and other data can be stored in the main memory130.

The processor110can also be connected to various interfaces via a system interface150, which can be an input/output (I/O) device interface (e.g., USB connector, audio interface, FireWire, interface for connecting peripheral devices, etc.). The processor110can also be connected a communications interface155. The communications interface155can provide the user device101with a connection to a communications network160. Transmission and reception of data, information, and instructions can occur over the communications network160.

The processor110can also be coupled to one or more data storage elements140and be arranged to transfer data to and/or receive data from the data storage elements140. The data storage element140can hold legacy data145, including any data or information previously obtained from other technologies or platforms. Although shown as having been included in the user device101, one skilled in the art should appreciate that the data storage140and/or legacy data145need not be included in the user device101. The data storage140and any storage component storing the legacy data145can be positioned in a remote (or independent) position from the user device101and/or the platform data converter137and connect to the user device101and/or the platform data converter137using any techniques known in the art. For example, the data storage140and any storage component storing the legacy data145can connect to the user device101and/or the platform data converter137through the communications network160.

Generally, the legacy data145can include any quantitative data obtained from data generation platforms, such as independent genomic data generation platforms physical and/or biological measurements and data generation for the purposes of predictive analytics. The legacy data can be data obtained using a genomic data generation platform such as RT-PCR, microarray sequencing, Bead Array microarray technology, proteomics, etc. These genomic data generation platforms are typically computationally intensive and require expenditure of massive resources to generate data that can be used in discovery and validation of biomarkers for applications, such as molecular pathology diagnosis. For example, a biomarker study using microarray data to give prognosis on a patient after surgery and radiation therapy for advanced stages of a disease (e.g., lung cancer) can cost millions of dollars. Such biomarker studies from older genomic data generation platforms, however, cannot be used in a more recently developed platform (e.g., on a Next Generation Sequencing hardware) because often the study results would not run on the hardware of a later developed platform. Naturally, this can render biomarker studies performed with more recently developed genomic data generation platforms inefficient because although all of these genomic data generation platforms are developed for detecting the same biological index or entity (e.g., gene expression), the generated results from these platforms cannot be mixed or combined for retrospective analysis.

The legacy data can include any data generated by the platforms, such as genomic data obtained using any platform or technology capable of generating genomic information. The term “genomic data,” as used herein, refers to, but is not limited to gene expression data. For example, the genomic data can be sequencing data obtained from sequencing a genome. The term “data sequencing,” as used herein, is used in its ordinary context in the fields of genetics, genomics, and bioinformatics and can be performed by any method or technique known in the art.

The legacy data can be obtained on one or more specific disease or disorders. For example, the legacy data can be obtained from on breast cancer or any other disease or disorder believed to be a genetic condition. The terms disease or disorder, as used herein, are intended to refer to their ordinary meaning. For example, the disease or disorder can be a genetic condition possibility resulting from one or more modifications, mutations, insertions, or deletions in the genome of a human individual.

The legacy data145can be pre-processed to ensure that it only contains data pertaining to a specific disease or disorder. For example, the legacy data145can be pre-processed to crop or filter all genomic sequence information other than information on the specific disease or disorder.

Further, the legacy data can be processed legacy data and include portions that have been associated with labels, markers, indictors, etc. The labels or indicators can be designated to portions of the data that include genetic information pertaining to a specific disease or disorder. For example, the legacy data can be data obtained on a specific disease or disorder, such as breast cancer. Further, as noted, the legacy data obtained on a specific disease (e.g., breast cancer) can include labels that associate certain portions of the data with labels indicating that those data portions include genetic information pertaining to a specific disease. For example, the legacy data can include a label that indicates a certain portion (e.g., one or more data samples) of the breast cancer data includes the gene signature for the BRCA1 gene, which relates to certain types of breast cancer.

It should be noted that the term legacy data, as used herein, is not necessarily intended to refer to older and/or existing platforms. One skilled in the art should appreciate that embodiments described herein are not necessarily limited to the usage of data from platforms in use or developed at an earlier point in time for understanding data obtained from platforms in use or developed at a later point in time. The embodiments described herein can generally be utilized to use data obtained from any platform (regardless of when the platform was implemented or used) to understand, interpret, or translate data obtained from that same platform, another similar platform, or another, possibly independent, platform. Accordingly, the term legacy data, as used herein, refers to genomic data that has been obtained on a specific disease or disorder and/or possibly processed to include labels, references, or indicators specifying certain genomic information that may be included in the data.

The legacy data can be data obtained from more than one platform. For example, the legacy data can include data portions obtained from two or more platforms. For example, the legacy data can include multiple subsets of data obtained from various microarray sequencing techniques and processed to include labels indicating existence of genetic information pertaining to a specific disease.

Returning to the user device101shown inFIG. 1, the user device101can also include a display160for receiving and/or displaying information (e.g., monitor, display screen, etc.). Although shown as an interactive system having a display, one of ordinary skill in the art should appreciate that the system100disclosed herein are not limited to embodiments implemented using a computer or implementation requiring direct interactions with a user. The system100can be implemented in chip or in any other electronic hardware known in the art and operate without requiring any interaction or feedback from a user170.

In the example shown inFIG. 1, a user170interacts with the system100through the user device101. The user170can provide the system100with information or request certain information from the system100. For example, if the legacy data145includes information from more than one existing or previous (legacy) platforms, the user170can select the one or more legacy imaging platforms (not shown) from which data and information are obtained. The user can be a medical professional, a scientist, a physician, a clinical, a patient, or anyone or any device that can make use of the information provided by the user device101.

The user device101and/or the processor110can also be connected to a current data acquisition technology or platform165. As shown inFIG. 1, the user device101can directly connect to the current platform165. Alternatively and/or additionally, the current platform165can be remotely coupled with the user device101and/or the processor110. For example, as shown inFIG. 1, the current platform165can connect to the user device101via the communications network160.

The current platform165can be any platform used for obtaining physical and/or biological measurements and providing information and data regarding the obtained measurements. For example, the current platform165can be a platform for obtaining quantitative gene expression data167using a Next Generation Sequencing technique, such as RNA-seq. The current platform165can generate data having lower, similar, or higher resolution than the legacy data. In some embodiments, the current platform165can be at least one of the platforms used to generate the legacy data145(dataset A). Specifically, the legacy data145can include data previously generated by the current platform and possibly processed to include labels identifying the genetic information relating to the specific disease or disorder. The legacy data145can be a quantitative dataset, having quantitative values (values A).

The current platform165can obtain the quantitative gene expression data167from genetic material181of a subject180, such as a human subject180. The human subject180may be an individual suspected as carrying the genetic information that generally indicate the predisposition for a certain disease or disorder. For example, the subject180maybe an individual suspected as carrying the BRCA1 gene, the presence of which generally indicates suitability for having breast or ovarian cancers. The quantitative genomic data167can be any quantitative data obtained from data generation platforms, such as independent genomic data generation platforms physical and/or biological measurements and data generation for the purposes of predictive analytics.

Further, the quantitative genomic data167can be obtained on one or more specific disease or disorders. For example, the quantitative genomic data167can be obtained from on breast cancer or any other disease or disorder believed to be a genetic condition. As noted with respect to the legacy data, the terms disease or disorder, as used herein, are intended to refer to their ordinary meaning. For example, the disease or disorder can be a genetic condition possibility resulting from one or more modifications, mutations, insertions, or deletions in the genome of a human individual. Furthermore, the quantitative genomic data167can be pre-processed (e.g., by cropping or filtering all information than information on the specific disease or disorder) to ensure that it only contains data pertaining to a specific disease or disorder.

Once the current platform165has obtained the quantitative genomic data167relating to the genetic material181, the quantitative genomic data167must be processed to determine whether it contains or lacks information that may be of interest. For example, any quantitative genomic data167obtained from a person suspected as carrying the BRCA1 gene would need to be processed to determine whether it contains or lacks information indicating the presence of this gene (e.g., the known gene signature for the BRCA1 gene). Clearly, processing the current quantitative genomic data167alone, without considering the information that may be available in the legacy data, can be inefficient. Specifically, it is more efficient for the current platform165to employ information previously obtained from similar datasets in processing the current dataset167. For example, it would be more efficient for the current platform165to use the gene signature generally produced by the BRCA1 gene (in other studies) to determine whether a similar gene signature exists in the current dataset167. However, as noted, often times previously generated (legacy) data145are tied to the platform on which the data are generated and cannot be readily used by other, independent, platforms.

The platform data converter137described herein remedies the inefficiencies caused by possible incompatibilities that may exist among the platforms by translating the legacy data145(e.g., data from previously existing platforms) into information that can be used by current platform(s)165to interpret and translate measurements obtained from the current platform(s)165.

One of ordinary skill in the art should recognize that the embodiments described herein can be used to analyze data obtained from the same subject or individual using various the same or two or more independent platforms. For example, embodiments described herein can be used to utilize information provided by first gene expression dataset, obtained from genetic material belonging to an individual, to understand and/or interpret another gene expression dataset, belonging to the same individual. The two datasets can be obtained from the same genomic data generation platform or from independent platforms. For example, the first dataset (dataset A) can be a gene expression dataset, obtained from a patient on a specific disease or disorder, using a first platform, and the second dataset (dataset B) can be a another gene expression dataset, obtained from the same patient, using the same or a second platform. The first dataset may be a dataset that has been already analyzed to determine whether it contains information pertaining to the specific disease or disorder. The information from the analysis of the first dataset can be used to understand the second dataset and/or to determine whether any modifications, mutations, insertions, or deletions in the genome of the patient have occurred.

The current platform165can be directly connected to the user device101and the platform data converter137. Alternatively or additionally, the current platform165can be remotely connected to the user device101and the platform data converter137, for example through the communications network160. Therefore, the platform data conversion and translation capabilities offered by the platform data converter137can have immediate application in clinical domain and genomics because it can provide significant cost saving in predictive analytics design and validation. The platform data conversion and translation capabilities offered by the platform data converter137can also be applied in other areas of clinical and technical domains or data processing, for example in biomedical imaging.

The platform data converter137uses a specific data transformation based on rank ordering and relative distance to formulate a sequence of procedures for predictive modeling and/or pattern recognition. The terms “rank ordering” as used herein refers to the ordinary meaning of this term as used in the art (e.g., as used in the field of statistics). More specifically, the term “rank ordering” refers to a type of data, in which quantitative, ordinal, or numerical values of data samples (data values) are replaced by their rank when the data sample are sorted.

The platform data converter137can accept the legacy data as a training dataset. The training dataset includes samples of quantitative genomic data values and associated labels, generated on a specific genomic platform (legacy platform (not shown)) on a specific disease or condition (e.g., breast cancer). The terms “training dataset” or “training set,” as used herein, refer to the ordinary meaning of these terms in the fields of machine learning, intelligent systems, and statistics. Generally, the terms “training dataset” or “training set” are used herein to refer to dataset used to find potentially predictive relationships.

The platform data converter137can also accept a sample or a set of samples of quantitative genomic data values (current quantitative genomic data167, data values B) generated on a different genomic platform (current platform165) for the same disease or condition. For each sample and each data value from the legacy data145, the platform data converter137can compute associated value rank (VR) and/or an associated rank-specific percentage of sample range (RSPSR). Specifically, the value rank can be a rank assigned to each sample based on quantified measurement value of that sample. For example, the value rank can be assigned by ranking the samples based on their quantitative samples values from highest to lowest. The RSPSR can be the relative (e.g., Euclidean) distances among the samples, normalized by sample value range in the sequence of ranked feature values.

The platform data converter137can further form a predictive model using any technique known in the art, for example, Logistic regression, Random Forest, etc. In this way, the legacy data145is converted into transformed and/or normalized version of itself, such that an intensity plot of the data points in the legacy data145and an intensity plot generated based on the corresponding VR (VR plot) and/or RSPSR (RSPSR plot) values for each data point present similar intensity characteristics. The predictive model can be formed using data from the same patient/individual using different platforms, such that the predictive model is exclusive to a single patient.

If the data points in the legacy data145(values A) have been previously labeled, the labels associated with the data points in the legacy data145are assigned to corresponding points in the VR plot or the RSPSR plot. If labels are not available, representative clusters of data in the VR plot and the RSPSR plot are identified. The representative clusters can be identified based on the VR and RSPSR values, for example, by clustering points having similar or similarly distributed VR and RSPSR values into the same cluster. Once the representative clusters are identified, the identified clusters can be used as classification features and any labels previously associated with the data points in the representative clusters is assigned to the clusters. The VR, RSPSR, identified clusters, and associated labels can be used to form a predictive training model.

Similarly, for each sample in the current genomic dataset167(values B), the platform data converter137computes associated VR and RSPSR values. The calculated VR and RSPSR values are applied as the test data to the training and predictive model previously formed using the VR, RSPSR, identified clusters, and associated labels of the first quantitative gene expression dataset. The predictive labels predicts labels for the current dataset167and/or identifies associated clusters in the current dataset167.

FIG. 2is a block diagram of procedures that can be used by the platform data converter137to convert the legacy data145into data that can be utilized by current platforms165in translating, interpreting, and/or understanding the information acquired using the current platforms165. As shown inFIG. 2, the platform data converter137utilizes quantitative genomic data201-A generated by legacy genomic data generation platforms205-A. The data201-A can be obtained directly from legacy genomic data generation platform(s)205-A or from databases209-A that store such information. The legacy genomic data generation platform205-A can be any platform or technology that can obtain physical and/or biological measurements of a biological specimen (e.g., tissue sample) and generate information regarding the biological specimen. For example, the legacy platform205-A can be a platform for obtaining quantitative gene expression data using a DNA microarray. The information obtained from the legacy genomic data generation platform(s)205-A can be stored in a database209-A that stores such information.

The database209-A can be a single database that stores quantitative genomic data from a select number of legacy platforms205-A or select number of databases that store legacy data. Alternatively and/or additionally, the database209-A can be a collection of two or more databases (not shown), each of which stores genomic sequencing information obtained from one or more legacy genomic data generation platforms.

Similarly, the platform data converter137can obtain quantitative gene expression data from current genomic data generation platforms205-B. The current genomic data generation platforms205-B can be any platform that can obtain physical and/or biological measurements of a biological specimen (e.g., tissue sample) and generate information regarding the biological specimen. Although described as a more recently developed platform that utilizes data obtained from legacy genomic data generation platforms, one skilled in the art should appreciate that embodiments described herein are not necessarily limited to the usage of data from platforms in use or developed at an earlier point in time for understanding data obtained from platforms in use or developed at a later point in time. The embodiments described herein can generally be utilized to use data obtained from any platform (regardless of when the platform was implemented or used) to understand, interpret, or translate data obtained from another, possibly independent, platform.

The data210-B obtained from the current genomic data generation platform205-B is stored in a database209-B for use by the platform data converter137. As noted above, in place of obtaining the data201-B directly from the current genomic data generation platform205-B, the database209-B can obtain the data from other databases that store such information. Alternatively and/or additionally the database209-B can be a collection of two or more databases that store quantitative genomic data.

The quantitative genomic data210-A,210-B from the previously existing and current platforms is forwarded to the platform data converter137. The platform data converter137accepts the data210-A,201-B and proceeds by extracting portions of the legacy data201-A that pertain to a specific disease or disorder (e.g., breast cancer or lung cancer) (box220). The specific disease or condition can be any condition or disease that is of interest to a user170(FIG. 1) utilizing the platform converter data137. Alternatively and/or additionally, the platform data converter137can obtain quantitative genomic data that has been previously labeled as being related to a certain disease or disorder from the database209-A. In such cases, the platform data converter137does not need to perform any additional processing and can directly obtain the data associated with a particular disease or disorder and any associated labels (e.g., labels indicating the association of the data with the specific disease or disorder) from the database209-A.

The platform data converter137also accepts data210-B generated on a different platform (e.g., current platform205-B) for the same disease or condition. The data210-A, obtained from the legacy platform is processed and a score is assigned to each data sample or data point in the dataset210-A (box230-A). For example, the platform data converter137can assign a value rank (VR-A) and a rank-specific percentage of sample range (RSPSR-A) to each data point included in dataset210-A. The value rank is assigned to each data sample by assigning an index value or score to each sample of the data. Specifically, given that that the platform data converter is processing quantitative data values, each sample of the data already includes or is associated with a quantitative measurement value. Therefore, to assign a value rank to the data samples, the platform data converter137can evaluate the quantitative measurement values and assign a rank or score to each quantitative value. For example, assuming that the quantitative data included in legacy dataset201-A is denoted by F and includes data sample values each denoted by fi, where F={fi|i=1, . . . , N}, the platform data converter137can assign a set of ranks VR, where VR={VRi|i=1, . . . , N}, to each data sample.

The platform data converter137can also assign a rank-specific percentage of sample range (RSPSR-A) to each data point included in dataset210-A. The RSPSR-A can be a normalized measure of the VR-A values assigned to each dataset. For example, the RSPSR-A can be the relative Euclidean distances of the sample values normalized by sample value range in a sequence of ranked feature values.

Similarly, the platform data converter137assigns a value rank (VR-B) and a rank-specific percentage of sample range (RSPSR-B) value to each data point in the dataset210-B obtained from the current genomic data generation platform205-B. As noted, given that the platform data converter137is analyzing quantitative genomic data, each sample of the data already includes or is associated with a quantitative measurement value. Therefore, to assign a value rank to the data samples, the platform data converter137can evaluate the quantitative measurement values and assign a rank or score to each quantitative value.

The platform data converter137uses the VR-A and RSPSR-A values assigned to the data samples201-A obtained from the legacy platform to form a predictive model (box240-A). The predictive model240-A can be implemented using any predictive modeling scheme known in the art. For example, the platform data converter137can employ a predictive modeling that employs logistic regression, Random Forests, or any other machine learning modeling known in the art.

The predictive model240-A can use the assigned ranks (VR-A) and rank-specific percentage of sample ranges (RSPSR-A) to label the data201-A obtained from the legacy platform205-A. Since some of the data can already be labeled (e.g., include labels associating certain portions of the data with a specific disease or disorder), the predictive model240-A need not to label all data. However, the predictive model240-A assigns labels to portions of the data210-A that have not already been labeled. Specifically, the platform data converter137identifies representative clusters (RC) in the ranked data and assigns labels to the portions of data included in the representative clusters.

The clusters of data are identified using the VR-A and RSPSR-A scores. Specifically, the platform data converter137identifies portions of data in which the VR-A and/or RSPSR-A scores appear to have similar values and create evenly or near-evenly distributed intensity clusters. The platform data converter137assigns labels to these evenly or near-evenly distributed clusters and assumes that each of these clusters can correspond to a specific gene, collection of genes, gene signature, and/or genomic information that identify the specific disease or disorder on which the legacy data201-A was generated.

It should be noted that since the legacy data210-A includes data that has already been sequenced and processed, the identifying labels (or at least some information about the labels) are often already available to the platform data converter137. For example, assuming the specific disease or disorder is breast cancer, the quantitative genomic data are provided to the platform data converter137with certain portions of data having already been labeled as identifying a breast cancer related gene, such as the BRCA1 gene. After processing the quantitative genomic data and assigning the VR-A and RSPSR-A scores, identifies data clusters (i.e., portions of data in which the VR-A and/or RSPSR-A scores appear to have similar values and create evenly or near-evenly distributed intensity clusters) corresponding to the portions already labeled as identifying the specific gene (e.g., the BRCA1 gene) and notes the VR-A and RSPSR-A values assigned to these clusters.

Alternatively and/or additionally, if there are portions of the data that have not been already labeled, the platform data converter137assumes that these data portions must have been attributed by a specific gene, gene signature, and/or genomic information and assigns a label to that portion of the data, identifying the data portion as corresponding to a specific genomic information. The platform data converter137can assign the data labels using information previously obtained from the same platform or other independent platforms.

For example, the platform data converter137can access a library that stores average value ranks and rank-specific percentage of sample ranges obtained from other genomic experiments using the same platform (as the dataset at hand) for the same disease or condition, obtain labels previously assigned to clusters having similar value ranks and rank-specific percentage of sample ranges as the unlabeled portions, and assign those labels to the unlabeled portions. Alternatively and/or additionally, the platform data converter137can access libraries that store normalized value ranks and rank-specific percentage of sample ranges obtained from genomic experiments performed using other independent platform for the same disease or condition, obtain labels previously assigned to clusters having similar normalized value ranks and normalized rank-specific percentage of sample ranges as the unlabeled portions, and assign those labels to the unlabeled portions.

The platform data converter137can also use the VR-A and RSPSR-A values to form a training model (not shown). The training model can be a part of the predictive model240-A. The training model can admit the VR-A and/or RSPSR-A values assigned to the data point in the legacy dataset210-A and their associated labels as training information. The training model can use this training information to form a predictive relationship for predicting labels that should be associated with clusters of data in dataset obtained from other, independent, genomic data generation platforms. The training model can be formed using any training technique known in the art, for example the training model can be formed using at least one of regression analysis, Random Forest, machine learning techniques, etc.

As noted above, the platform data converter137assigns a value rank (VR-B) and a rank-specific percentage of sample range (RSPSR-B) value to each data point in the dataset210-B obtained from the current genomic data generation platform205-B. The platform data converter137can apply the training model to the VR-B and RSPSR-B values assigned to the dataset210-B to identify clusters of data in the dataset210-B having similar VR-B and RSPSR-B intensity values and/or patterns. Once clusters having similar VR-B and RSPSR-B intensity values and/or patterns are identified, labels associated with these clusters in the training dataset are assigned to the identified clusters (box260).

FIG. 3is a flow diagram of procedures that the platform data converter137can use to assign labels to data portions included in a quantitative genomic dataset obtained from a current platform. As shown inFIG. 3, the platform data converter137can access quantitative legacy genomic data obtained from other independent genomic data platforms (box310). The obtained data can be arranged such that it already relates to a specific disease or disorder (e.g., breast cancer). Alternatively or additionally, the platform data converter137can extract portions of the data that relate to a specific disease or disorder from the legacy dataset (box320).

The platform data converter137can rank each data sample in the legacy data and assign a value rank (VR-A) or score to each data point (box330). As noted, since the legacy data is presented to the platform data converter137in the form of quantitative data, with each data point having a quantitative value, the platform data converter137can assign rank scores to the data points based on their respective quantitative values (box330). The platform data converter137can also assign a rank-specific percentage of sample range (RSPSR-A) to each data point included in legacy dataset (box340). The RSPSR-A can be a normalized measure of the value ranks assigned to the legacy dataset. For example, the RSPSR-A can be the relative Euclidean distances of the sample values normalized by sample value range in a sequence of ranked feature values.

The platform data converter137can identify clusters of data having similar, evenly distributed, or near evenly distributed intensity values and assign labels to each cluster (box345). As noted above, some of the data can already be labeled (e.g., include labels associating certain portions of the data with a specific disease or disorder). Therefore, the platform data converter137need not to label all data and can limit assignment of labels to portions of the legacy data that have not already been labeled.

The value ranks, RSPSR-A values, and the labels associated with each cluster can be used to form a predictive model (box350). The predictive model can be a training model that admits the value ranks, RSPSR-A values, and the labels associated with each cluster as training information. The training model can use this training information to form a predictive relationship for predicting labels that should be associated with clusters of data in dataset obtained from other, independent, genomic data generation platforms. The training model can be formed using any training technique known in the art, for example the training model can be formed using at least one of regression analysis, random forest, machine learning techniques, etc.

The platform data converter137can develop a predictive training model using the value ranks and the RSPSR-A values assigned to the legacy dataset. The predictive training model can be developed using any training technique known in the art. For example, the training model can be formed using at least one of regression analysis, random forest, machine learning techniques, etc. The training model can admit the value rank and/or RSPSR-A values assigned to the data point in the legacy dataset and their associated labels as training information to form a predictive relationship for predicting labels that should be associated with clusters of data in dataset obtained from other, independent, genomic data generation platforms.

The platform data converter137can also acquire unanalyzed/unlabeled quantitative genomic information from another, independent genomic data acquisition platform (box315). For example, quantitative genomic data can be obtained from a platform having capabilities not offered by the platforms that are used to generate the legacy data. For example, the current platform can be a platform that produces data having higher resolutions than data typically generated by the legacy platform.

The data obtained from the current platform can be arranged such that it already relates to a specific disease or disorder (e.g., breast cancer). Alternatively or additionally, the platform data converter137can extract portions of the data that relate to a specific disease or disorder from the legacy dataset.

The platform data converter137can rank each data sample in the legacy data and assign a value rank (VR-B) or score to each data point (box335). The platform data converter137can assign rank scores to the data points based on their respective quantitative values (box345). The platform data converter137can also assign a rank-specific percentage of sample range (RSPSR-B) to each data point included in dataset obtained from the current platform (box355). The RSPSR-B can be a normalized measure of the value ranks assigned to the dataset. For example, the RSPSR-B can be the relative Euclidean distances of the sample values normalized by sample value range in a sequence of ranked feature values.

The platform data converter137can apply the rank (VR-B) and the RSPSR-B values obtained from the data as a test dataset to the training model so that the training model can identify clusters of data in the dataset210-B having similar VR-B and RSPSR-B intensity values and/or patterns (box355). Once clusters having similar VR-B and RSPSR-B intensity values and/or patterns are identified, labels associated with these clusters in the training dataset are assigned to the identified clusters (box365).

As noted, embodiments disclosed herein are not limited to use with genomic data generation platforms and can be used with other data acquisition platforms, such as medical image acquisition platforms. For example, embodiments disclosed herein can be utilized to translate information already obtained from a medical image to understand and interpret information in medical images obtained from another, possibly independent, platform.

FIG. 4is a table that includes prediction results obtained using embodiments described herein. The results shown in the table are obtained by considering quantitative gene expression data obtained using a Microarray platform (platform 1) and quantitative gene expression data obtained using an RNASeq gene expression platform. The data are generated on breast cancer patient. Specifically, data are obtained on 50 genes in 508 patients with Breast Carcinoma from the cancer genomic atlas (TCGA) with available subtype labels (e.g., Basal, Her2, LumA, LumB). The dataset obtained from the microarray platform was used to construct the training data on the predictive model described herein. The prediction results are subsequently validated on RNASeq data.

Specifically, the microarray data are validated by computing VR and RSPSR feature values for microarray data of 50 genes in all patients. These values are used as a first feature set in the analysis. The VR and RSPSR values for RNASeq data points obtained on 50 genes in all patients. These values are used as the second feature set in the analysis. A predictive model is then developed for each individual patient. For example, for each individual patient, a one-leave-out Random Forest model (having ntrees=500) using the first feature set, excluding given patient training point.

The predictive model is used to predict each individual patient subtype using the model and corresponding feature values from the second feature set. As shown inFIG. 4, from 94 samples of Basal, 91 samples were correctly identified. Similarly, from 57 samples of Her2, 41 samples were correctly identified. From 231 samples of LumA, 149 samples were correctly identified and from 126 samples of LumB, 123 samples were correctly identified. The inaccuracies (e.g., genes that were incorrectly classified, for example 3 Basal genes classified as LumA) are believed to be due to insufficient number of samples and existence of noise in the data.

While the invention has been particularly shown and described with reference to specific illustrative embodiments, it should be understood that various changes in form and detail may be made without departing from the spirit and scope of the invention.