Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
  • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
  • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
  • G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
  • G01N33/6842—Proteomic analysis of subsets of protein mixtures with reduced complexity, e.g. membrane proteins, phosphoproteins, organelle proteins
• • G—PHYSICS
  • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
  • 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
  • G16B25/10—Gene or protein expression profiling; Expression-ratio estimation or normalisation
• • G—PHYSICS
  • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
  • 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

Definitions

• This invention relates generally to genomic or proteomic testing. More particularly this invention provides a system and method for measuring the expression of the genome and other biological factors over a network, which could lead to disease prediction and prevention in humans.
• Background Of The Invention Mapping of the human genome has been in process by both the government and private industry for the past ten years. At the same time new research has lead to specific tests for conditions that are evidenced by genes and certain gene expressions. Further the methods for the detecting of genomic, proteomic and other biological factors have dramatically improved.
• genetic engineering and research is extremely active in the agricultural marketplace where both plants and animals are the subject of genetic engineering and commercialization.
• RNA and protein chips available from, for example, Ciphergen which will allow genes, their expression and proteins to be identified on a particular chip.
• Micro Arrays such as those of Nycomed Amersham / Amersham Pharmacia Biotec allow gene detection via very small detectors, thereby reducing the size of the overall detector package.
• fiber optic probes for example by lllumina, Inc. now allow 250,000 discrete sensors to fit on a probe the diameter of a pin head for proteomic studies.
• Nanogen possesses electronic concentration and hybridization technology that is suited to the present invention.
• Such technology is embodied in a disposable cartridge comprising a semiconductor microchip and electrical and fiuidic connections for use in analysis equipment.
• U.S. patents discuss this technology, the contents of the below listed patents are incorporated herein by reference in their entirety: U.S. Patent No. 6,099,803 "Advanced active electronic devices for molecular biological analysis and diagnostics " U.S. Patent No.
• the present invention comprises a plurality of analysis devices and other detection means that can be produced and distributed to individuals and professionals in the human sciences in great quantities. It is the intention of the present invention to produce such analysis devices in sufficient quantities so that they can be made available to all who desire them in a cost effective fashion. Over time it is expected that the cost of such analysis devices will decrease dramatically and therefore allow analysis devices to be available to anyone desiring to characterize the expression of their genome or other biologically related information.
• analysis devices are used by a person for determining the person's own control or "standard" expression profile of their genes or other biological indicators that are to be monitored.
• the individual simply provides a blood, saliva, or urine sample as obtained and placed in / on the analysis device.
• the analysis chip for example, contains probes for all human genes linked to the surface of the chip.
• Such chips are capable of detecting the presence of other nucleic acids (specifically messenger RNA) which are present in the solution via homology hybridization.
• Analysis Chips may contain small fragments of the genes (oligonucleotides) or expressed sequence tags (ESTs) or RNA molecules or their fragments as well as proteins or their fragments. Other detector devices will have similar mechanisms for detecting the biological indicator of interest.
• a "lab-on-a-chip” with microchannel separation of biological materials (DNA, RNA, protein, hormone, small molecule, peptide, metabolite) with subsequent electrochemical or electric, such as those of Clinical Micro Sensors or optical, such as those of PharmaSeq detection.
• Such technology also includes 3D silicon particles of cubic or spheric shape, which could carry detection molecules (DNA, RNA, antibodies).
• PCR polymerase chain reaction
• PCR polymerase chain reaction
• the expression or recording of these biological indicators can then be digitized or put in some other transmittable form at home or at a convenient location on the analysis device reader or other device to make the genetic expression or recording of biological indicators of the individual in the form that is transmittable via the network.
• a digitized record of the expression profile of the genome of the human which includes transcriptome (all molecules of RNA expressed in the cell as well as in the body), proteome (i.e. the proteome is the summary of all proteins of the human being) or other biological indicator is then created.
• the hand held device or computer attached device or real time monitoring station will detect genetic variations of the humans including, but not limited to, Single Nucleotide Polymorphisms (SNPs) as well as genetic variations in genes of another nature. Those will be compared for a particular individual for himself/herself over time - giving a chance to build a time- correlation of the progression of the disease. Clinical data will be used to compare populational data of norm versus disease. SNPs could be detected in devices developed by Hyseq or Sequenom, or other manufacturers. Genetic variation noted above can be accomplished on a general basis where many genes are detected and analyzed or, when suggested via background or family history, on a specific SNP analysis based upon expression work done previously.
• SNPs Single Nucleotide Polymorphisms
• an analysis and database site exists on a network, preferably but without limitation on the Internet, that has extensive information on the human genome and the meaning of various genetic expressions and mutations as well as metabolism maps.
• An individual wishing to have his or her expression profile reviewed, read, and interpreted will send a digitized record created at the analysis device reader over the Internet, or via some other wired or wireless network to the analysis site.
• the software routines for analysis and interpretation at the analysis site will then read the digitized or transmittable record and interpret that record providing feedback to the individual over the Internet, over an intranet, a wireless network or via any other means (such as voice) for conveniently reporting such information to the individual.
• an individual can provide a new series of digitized or otherwise recorded biological indicators to the analysis site central database and determine how the person's expression profile is changing. This may suggest certain interventions on the part of the individual
• the present invention provides for a flexible series of methods and associated apparatus allowing individuals to create a record of their gene expression (RNA and protein) to broaden profiles and other genomic and biological information in a convenient fashion.
• an analysis device reader to be attached or connected to the individual's PC for subsequent reading and providing information over a network, which is preferably, but without limitation, the Internet.
• analysis device readers may be located in physicians' offices to provide such information for subsequent analysis when a personal computer and analysis chip reader is not available.
• Yet another alternate embodiment allows for a single purpose analysis device reader which can provide genetic information over a network.
• a device may be a diabetes screening chip, sex hormone analysis chip, or other single purpose device optimized to look for a specific gene, metabolite or other indicator of a condition.
• Yet another alternate embodiment allows for the wireless presentation of analysis device information over a radio network, for example over a cellular network.
• a form of wireless or cellular type device hereinafter referred to as a genophone, allows genetic or other biological information to be provided over wireless and/or cellular type networks to an analysis center.
• Yet another alternate embodiment of the present information allows for a kiosk type operation whereby an analysis device dispenser is located in a public area, such as a mall, HMO, hospital or indeed any other public area.
• an individual would simply use a credit card or, preferably a smart card having specific encrypted identification information, that is linked to a credit card processing company such as American Express ®, VISA®, MasterCard®, or other for billing services.
• the individual simply inserts the credit/smart card and, after credit verification, would receive an analysis device upon which a biological sample could be deposited by the individual.
• the analysis device would then be read by the kiosk analysis device reader and information from the reading sent to the analysis site.
• an individual can enter information either at the kiosk location or, using coded information that is present on the smart card, the individual can cause the results of the analysis to be sent to the individual via the US Mail, via electronic mail, or via any other selected delivery service which the user prefers including voice transmission to a selected telephone number or voice mail.
• the results of the analysis is sent to the individual via the US Mail, via electronic mail, or via any other selected delivery service which the user prefers including voice transmission to a selected telephone number or voice mail.
• information is sent to the person involved together with information on how to locate source to assist in proper interpretation or the data.
• identification of counseling or scientific resources would also be identified depending upon the outcome or projected outcome to help the individual understand the results received.
• the present invention also comprises a genome and heafth information- specific encrypted browser for individual use.
• This browser when used with the personal computer or in use with video phones or the like, allows genomic and other biological information from the individual to be appropriately delivered directly to an analysis site as well allows rapid and encrypted access to specific medical and gene analysis sites. In this fashion individuals will not need to expend significant effort in browsing the World Wide Web for information to support conclusions or preliminary analyses made concerning the individuals expression profile.
• the individual can access a database of genomic and other biological information of the present invention that comprises the individual's control expression profiles and management of the individual's medical information, all of which will be encrypted.
• a database of metabolic pathways which will be used to characterize the protein or other expression molecules and characterize and tell what role the protein that is detected has in the overall health- picture of the individual.
• a human genome sequence comparison database is also a part of the present invention and allows individuals' control expression profiles as well as subsequent expression profiles to be compared to various standard expression profiles for analysis purposes. Further, the database will contain subsequent databases and/or links to clinical data, clinical trials in practice, "live" consulting with experts as well as chat rooms to discuss with other individuals genomically, biologically, and medically important information.
• the database of the present invention comprises Single Nucleotide Polymorphisms (SNP), DNA sequencing, protein- protein interactions and protein-drug interactions so that individuals who generate a expression profile (protein and other molecules) can review what potential drug interactions might be specific for that individual.
• SNP Single Nucleotide Polymorphisms
• Any information that an individual wishes to store that is particular to the individual's concern (whether personal) can be stored in the individual storage area of the database in an encrypted form so that only the individual who has placed that data in the database can have access to the data.
• the genophone described above will have a series of capabilities. For example it will be able to read DNA or RNA using an appropriate DNA or RNA chip and transmit that information over the wireless network to the analysis center. These chips mentioned above are not meant as a limitation.
• the genophone will have a separate protein analysis cartridge, including those which could have antibodies, enzymes or other protein detection systems and separate sugars (or other biological molecules specific for humans) analysis cartridge each of which will be capable of receiving the associated device for deposit of a sample and analysis of the proteins, sugars and other metabolites as appropriate. It is further anticipated that these cartridges could be integrated into one single cartridge or unit.
• This "cartridge” can be a variety of forms and the form is not meant as a limitation. In other forms it employs the various detection technologies discussed (above).
• the cartridge may be a attachment to the genophone, or it may be its separate instrument or device with its own communications capability for providing information over a network.
• Cartridge may have different sets of detection mechanisms specific for a particular gene of the gene product or group of genes and their products, which could lead to different types of diseases, (i.e., a cartridge for monitoring gene expression which could lead to diabetes or cancer).
• Cartridges with different types of disease "preventive" expression and other monitoring could combine different types of diseases on one cartridge.
• specific disease state monitoring can be accomplished by the equipment of the present invention. Thus monitoring diabetes, fertility issues (hormonal variations) and other conditions can be monitored.
• a GeneChipTM is an analysis probe array manufactured by Affymetrix® which can detect MRNA transcripts at a few copies per cell. It can also identify concentration levels and simultaneously monitor thousands of genes. This GeneChipTM system is typically scanned by an HP GeneArray scanner to view an expression analysis.
• Yet another potential technology for analysis is the Assembled ArrayTM manufactured by lllumina, Inc. This array provides thousands of sensors to analyze DNA, RNA, and protein. Yet another example of chip analysis technology is the ProteinChipTM which is available from Ciphergen. Other analysis devices such as the GeneChipTM instrument system, also available from Affymetrix which provides a platform for analyzing GeneChip probe arrays. In short, certain of the building blocks are readily available for the present invention.
• Figure 1 illustrates the overall architecture of the present invention
• Figure 1A illustrates the stand-alone analysis device reader
• Figure 2 illustrates the genophone embodiment of the present invention
• Figure 3 illustrates the kiosk embodiment of the present Invention
• the present invention is a system and method for creation of expression profiles of individuals, establishing a control expression profile for an individual, and comparing subsequent expression profiles to the control expression profile for analysis purposes.
• the procedures when dealing with human genomic information will be discussed. Any reporting that is done will be in terms of the individual in question.
• individuals will initially provide a control biological sample on analysis devices 22, 24,and 26.
• analysis devices will be input to analysis device readers 16 which, in one instance are connected to PCs 14, 20 at user locations. It is also considered to be within the scope of the present invention to have an analysis device reader / communicator 28 which is a stand-alone unit that reads analysis device 26 and provides that information over the Internet 18 or some other wired or wireless network adapted to convey such information or analyze the biological sample "on the spot" providing limited read out of the presence and / or quantity of the expression of gene or other biological factors, for example and without limitation, particular proteins and their amount (See Figure 1A below).
• an intranet may be constructed to send and receive such information among a variety of sites at a hospital, or other large organization.
• a military organization has particular interest in the health and welfare of its forces.
• Analysis device reader 16 reads analysis devices 22, 24 and presents a digitized, or otherwise transmittable record of the individual gene expression or other biological information to the PC 14, 20 at the users location.
• the "users" location may be a home based unit or a unit at a convenient location such as a doctor's office.
• These PCs will further comprise software for communicating with the analysis site.
• connections to the Internet for reporting of these gene expression readings will be both wired as in the case of processor 20 connecting to Internet 18 and wireless as in the case of processor 14 connecting to a wireless fashion to Internet 18 or via other wireless special purpose devices optimized for the expression profile reporting of the present invention.
• the individual expression profiles will then be provided to an analysis site 12 over a network such as, and without limitation, the Internet 18 and stored in database 10 identifying the record only in a numeric fashion in order to preserve the unanimity of the individual providing the information.
• the individuals can report as many different gene or other biological expressions as desired since those expressions will vary by the time of day, over a period of years, and with changing individual conditions.
• Analysis site 12 receives the information from each individual and based upon expression, protein, messenger RNA etc.
• the analysis site 12 can create a reading of the gene expression of the individual together with an interpretation of any particular conditions that might exist. Information relating to the interpretation of the gene expression of the individual is then provided by analysis site 12 over the Internet 18 back to the individual's processor 14, 20 for the person's information. Alternatively, information from the interpretation of the genomic expression can be provided to the user via mail. It is expected, that as analysis device prices decrease, such analysis devices will be readily available at a reasonable cost to all individuals who desire to use this process.
• each individual's genes will be sequenced (all or in part) which will allow the creation of the "Individualized Analysis Devices.” Those will be used not only to establish individuals control and to obtain the genome expression reading, but to track any individual changes in persons genes. The difference in the expression of the individuals genes as well as detection of the specific changes (including but not limited to mutations) may unravel the condition in the event that the individual does not feel well, as they age, and as other significant events occur which may affect the individual's overall health. All results from individual analysis device readings will be stored in the biological database for access by the individual or his/her healthcare provider over time.
• the analysis device may be used for detecting any endemic viral or bacterial gene or other biological expressions occurring in the individual's body, which could result in disease or other malfunction of the body.
• medications and treatments can be recommended to an individual that will be best suited to change or correct that individuals gene expression or deal with a manifested condition. For example there may be a gene expression, which predisposes an individual to react adversely to certain medications or treatments. Similarly there may be certain protein-drug interactions about which an individual should be wary.
• recommendations for medication and treatments can be made to the individual.
• target drugs could be designed which work in an optimal fashion for the particular individual, as well as target “preventive” drugs.
• effectiveness of certain medications also depends upon the gene expression of the individual. In this case information can be provided to an individual as to which medications are best suited for that individual in a particular situation. From an economic standpoint, individuals will be able to purchase analysis devices 22, 24, and 26 at a reasonable cost once these chips are readily made available to millions of individuals. Each time a reading is interpreted by the genomic processor the individual can be charged for that particular interpretation. It is also anticipated that individuals will want to have their gene expression profile information stored anonymously in the analysis site database.
• the analysis device reader 16 in a stand-alone mode (as first noted above) is illustrated.
• a stand-alone analysis device reader 16 can be used.
• This analysis device reader uses the analysis device 24 to collect a biological sample.
• the analysis device 24 is placed in the analysis device receptacle 70, which is powered by a stand-alone power supply 62.
• This power supply can be single use or rechargeable battery supply, and may also be plugged into household current to recharge batteries or to simply power the stand-alone device.
• the analysis device reader 16 comprises analysis logic 64 for interpreting the analysis device readings. Thereafter, the reading may be stored in a memory 66 in the case where the user wants to have an historical record of readings over a period of time.
• the analysis device reader 16 also comprises a screen or display 68 for providing a limited readout of the presence of or quantity of the biologic factor or substance being collected by the analysis device 24. In this fashion, for example, if a particular biological factor is not present, and this is not troubling for the user, the results do not have to be sent over a network and risk a disclosure of the fact that such a test is being conducted by the user.
• the analysis device reader also comprises a communication port 68 which may be connected to a network for transmitting information stored in memory over the network as described in Figure 1 (above).
• the display, analysis logic power supply and readout capabilities are generally disclosed in U.S. Patent No. 5,837,546, which is incorporated herein in its entirety.
• the capability to analyze the genetic, proteomic and other biological factors described herein constitutes a novel capability within the current state-of-the-art.
• certain limited expression comparisons can be made from one reading to another.
• the analysis logic 64 can inform the user of the detection of that difference via the readout / display 68. Thereafter, if the user chooses that information can be sent to an analysis processor ( Figure 3, 12) via the comm. port 68.
• FIG 2 the genophone of the present invention is illustrated.
• the genophone 30 is a form of cellular communications device having its own transceiver 44 connected to the cellular network 45, which in turn subsequently is linked to analysis processor 12 via a wireless application protocol (WAP) gateway 47 and thence over the Internet 46 to the analysis site.
• WAP wireless application protocol
• the linkage to the analysis processor can also be via the wireless network directly where the analysis center is capable of receiving an electronic signal from the genophone over its own wireless transceiver or alternatively the genophone can ultimately connect to an Internet service provider via a WAP gateway, as noted above, and electronic information concerning data collected can then be presented to the analysis via the Internet as described earlier.
• the genophone has a series of cartridges or readers illustrated as sugar reader 32, DNA reader 34, and protein reader 36 although these readers are not meant as limitations. For example it is fully anticipated that as the bio/genomic science becomes more refined, other combination readers having this combinations or others are also anticipated. Each cartridge will have an associated analysis device illustrated as a sugar chip 38, a DNA chip 40 and/or a protein chip 42.
• FIG. 3 a kiosk-oriented embodiment of the present invention is illustrated.
• a form of kiosk 60 which would reside in a more or less public area such as a mall, a doctor's office, and/or a hospital.
• an individual possessing a credit card or, preferably, a smart card 62 which would be associated with a credit card issuer such as VISA®, MasterCard® and American Express® would have individualized identification information stored, in encrypted form, on the smart card 62.
• a credit card issuer such as VISA®, MasterCard® and American Express®
• An individual who wishes to establish a control expression profile or to simply create an expression profile at that point in time would use the smart card to begin the over all process of establishing an expression profile in much the same way that an individual now uses a credit card and automated teller machine to begin a financial transaction.
• the individual would insert the smart card 62 in the kiosk 60.
• the kiosk 60 is permitted to perform further functions. After the kiosk receives the appropriate authorizations from the credit facility for the financial aspect of the transaction, the kiosk provides analysis device 64 to the individual.
• the kiosk itself may be a cellular or wireless device that communicates with the analysis site in a wireless fashion.
• Information can be entered by the user at the kiosk regarding the location to which the information is to be sent.
• the user can specify that resulting information be sent to an associated e-mail address, be sent over the mail system to the user, to be reported via voice or delivered in other ways known to those skilled in the art.
• the kiosk can also communicate to the analysis center over a cellular or other wireless type network.
• the kiosk can report its results to the analysis via wired network, wireless networks, cellular networks, and other communications methods known in the trade including satellite communications as well.
• Encryption of the resulting data can be accomplished by an appropriate encryption key stored on the smart card of the individual and conveyed to the kiosk for subsequent encryption to the analysis center.
• individual expression profile information is kept in a secure fashion.
• the analysis processor of the present invention will review all files in its database and send the latest health news that relates to the diseases or conditions evidenced by the expression profiles stored in the database. In this fashion, and individual with, for example, diabetes, can receive the latest information that breaks relating to this condition or on the latest equipment available for maintaining a healthy state. Such information can be delivered via pager, wireless telephone, PDA, and or email.
• the organization that is responsible for the analysis processor will also receive notices of research projects requiring test subjects.
• the database of the present invention be searched and, if authorized by the affected individual, those whose conditions are to be the subject of such medical research will be provided notice of the need for test subjects. Again, in this fashion the database will be able to alert those with specific conditions or expression profiles of the opportunity to participate in such studies.
• the ramifications of this invention are significant. For example, while DNA, protein, mRNA, sugars and the like have been mentioned as items to be monitored, so can small molecules, peptides, hormones and metabolites. These items will also serve to establish a baseline when the individual is healthy and can later be monitored as potential precursors to a disease state(s).
• the information gleaned can be stored in an anonymous way in a database so that individual variation can be interpreted not just with respect to other measurements from the same individual, but can also be interpreted in the context of larger demographic results. Additionally, monitoring of those individuals undergoing therapy of various types is very important where there is a possibility of an adverse drug reaction or where a narrow therapeutic range is desirable for the drug in question. Real time monitoring of various indicators as noted in the present invention can help to avoid such adverse drug reactions.
• a genome and biological factor assessment apparatus and method in alternate embodiments has now been shown. It will be apparent to those skilled in the art that other applications and businesses can benefit from this model of DNA chip reading and genome information storage without departing from the scope of the invention as disclosed.

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