Curation

  • Rhythmus – prescribing clarity

    Rhythmus is a new app that makes prescribing natural agents simpler than before when using the Opus23 database of natural agent effects on genes.

    Taking an overview of all SNPs for the client, the main Rhythmus screen shows a list of genes sorted by combined SNP effect power factor, with the color scheme of orange for overall downregulated and green for overall upregulated genes. With over 7,800 individual associations of genes and natural agents in the database, all based on and hyperlinked to PubMed published studies, Opus23 makes visualisation simple for the genes with the highest editor-defined power factor and with associated natural agents that affect the gene function.

    Rhythmus Prescribing App

    Taking the Agency app one step further, Rhythmus also includes the gene visualising ability of Powerspot to help the practitioner choose the best agents for the clientThe AI Pre fills the option of upregulating or downregulating the gene function and the effect required from the agents (although these can be changed manually if required). The numbers of agents associated with the gene function is also listed.

    Rhythmus can be used by checking some genes and other options, then click the Run Rhythmus button. The result is a network map of the genes in the query along with the natural agents that influence their function.

    Rhythmus network map

    The relative size of the agent indicates the confidence of the effect on the gene, and as with other network maps on Opus23, clicking on the gene or agent opens a popup for that element, from where it can be curated to the Client Report or the Protocol Report.

    The AI saves time in selecting the best options according to the available data, but this can alway be overridden by the practitioner, who may have other information about the client. Opus23 subscribes to the philosophy of ‘TMTOWTDI’ (There’s more than one way to do it, pronounced ‘Tim Toady’.) The program was designed with this idea in mind, in that it ‘doesn’t try to tell the practitioner how to parse the data.’ Rather, it presents many different frameworks and cross-sections of the available client data, using a myriad of infographic treatments. Therefore Rhythmus also offers the practitioner a user-defined alternative visualisation of up to five manually entered genes, again with an up- or downregulatory effect and the required effect size. The user-defined visualisation gives a Manhattan map of the combined effect of the possible agents, similar to one side of the Psychic app.

    Result of the user-defined selection in Rhythmus

    As before, clicking on the agent opens the agent popup, where it can be curated. Rhythmus takes Opus23 to another level of utility for data mining and analysing its huge database of PubMed-based gene-agent interactions.

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  • Utopia Demonstration Video

    Dr. Peter D’Adamo and Dr. Tara Nayak present an introduction to Utopia, the free microbiome analysis add-on module to Opus 23 for uBiome test results.

     

    To use Utopia, you will need to  have your client’s 23andMe data already uploaded to Opus 23. You can then upload as many raw data files from uBiome tests as you have for that client. Utopia will work with individual uBiome tests, referencing the client’s 23andMe results where appropriate, and also give sequential analysis for multiple uBiome tests.

    The unique combination of Opus 23 and Utopia make this an opportunity for practitioners to get deep insight into their clients on both a genomic and a microbiological level, all sourced from published medical literature. The interaction between the two genomic analyses provides unparalleled informatics tools, and gives the practitioner an edge over any other genomic analysis tool available today.

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  • Utopia: Spectrum, visual community organization

    SPECTRUM: Visual community organization

    Utopia logo

    SPECTRUM provides a visual representation of the taxonomic data at both the genus and phylum levels. The app demonstrates the weight, influence and diversity of your client’s microbiome in two helpful display formats, each of which are clickable for a deeper look and easy report curation.

    Navigating  SPECTRUM

    Spectrum logo

    From the Utopia drop down menu, hover over ‘analytics’ until a second list appears, then select SPECTRUM.  Phyla and genus are displayed in pie chart format, which is accompanied by the spectrum profiler found below.

    The pie charts follow the color-coding conventions found in OPUS23 indicating beneficial, neutral as well as pathogenic organisms. Click on any desired section to open up its information pop—up window for detailed information including taxonomy, an overview of known disease or health benefit associations, descendants and metabolomics. Click ‘add/ curate’ to include it in your client’s report.

    Spectrum pie charts

    The spectrum profiler demonstrates the trends in your client’s biome diversity in a graphical format. Clicking on any of the category headings will open a pop-up window listing the organisms found in your client’s sample. Each genus listed is also clickable, opening a pop-up window for detailed information, including taxonomy, an overview of known disease or health benefit associations, descendants and metabolomics. Click ‘add/ curate’ to include it in your client’s report.

    Screenshot of Spectrum Profiler

    Metabolomics is a powerful addition to the spectrum profiler that provides a comprehensive list of metabolites associated with GI biome species. A list of all metabolites active in your client is included. Click on an individual metabolite for detailed information, including genera that are enhanced, inhibited, and those which generate the metabolite as an end product. Click on the Metabolomics link to open a pop-up with all active and inactive genera.

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  • Utopia: Loam, a fertile soil

    Announcing the launch of Utopia, the suite of apps within Opus 23 that analyzes and reports on sequential data from uBiome tests. uBiome is the world’s first sequencing-based clinical microbiome screening test, giving the user insight into the bacterial population of multiple body areas. Utopia recognizes all bacteria found by uBiome, but is specifically interested in the gut bacteria and its interaction with the client’s own genomic DNA. Utopia is free for existing clients: Once you have uploaded 23andMe raw data for your client, you can add as many uBiome tests as you want for that client without additional charge. Utopia will then give you access to multiple apps to analyze the data and reference it to the client’s genomic data where appropriate.

    Utopia logo

    LOAM: Adaptable taxon data

    LOAM is a highly flexible search and sort tool that allows you to easily navigate through your client’s Ubiome results by taxon. LOAM allows you to filter taxonomic data based upon several useful parameters as well as sort the filtered results. It is similar to the ARGONAUT app in Opus 23.

    loam

    Navigating LOAM

    From the Utopia drop down menu, hover over ‘analytics’ until a second list appears, then select LOAM. You will then be presented with the default table which shows ‘everything’ and is sorted by ‘repute’ or ‘interpretation’.

    At the bottom of the window is a jump screen that allows you to move from one screen to the next. You can control how many rows to display be selecting an option from the ‘Show’ pull down menu. The default is 15.

    Loam Screenshot

    Filtering and sorting results

    LOAM allows you to parse the taxon data based upon desired treatment goals. Taxons are sortable by benefit as well as pathogenic potential.

    The LOAM table displays the following data by column:

    • Taxon name
    • Repute, displaying beneficial !, neutral ! and pathogenic ! 
    • Rank
    • Client-specific % population
    • Average % (if available)
    • Standard deviation (if available)
    • Interpretation (displayed up to +6 times the standard deviation, populations found in a greater abundance are indicated by )
    • Normal variance
    • Order magnitude

    Click on any desired taxon to open up its information pop—up window for detailed information including taxonomy, an overview of known disease or health benefit associations, interactions and metabolomics. Click ‘add/ curate’ to include it in your clients report. The Curated column will then show a green checkmark against all curated taxon after refreshing the page. 

    LOAM columns are sortable. Click on any column title to sort by that column. Click that column again to reverse the sort order.

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  • A Roster of Opus 23 Algorithms

    This is a current list of the multi-snp algorithms currently available in Opus 23. A few titles repeat, for the simple reason that two different algorithms, using different snps or genes, can result in a similar conclusion.  Algorithms can be quite complex: it is not uncommon for one algorithm to call another algorithm as part of its execution. Algorithms are discussed in the blog post describing the Opus 23 LUMEN app.

     

    Classic Genetics

    • AB blood group
    • Blood Type O
    • A blood group (genotype AO)
    • A blood group (genotype AA)
    • A1/A2 blood group
    • B blood group (genotype BO)
    • B blood group (genotype BB)
    • Rhesus (Rh) blood group
    • Secretor
    • Non Secretor
    • Slight PTC Taster
    • PTC Non-Taster
    • Kell K/k blood group carrier
    • Duffy blood group positive (Fy+/+) / higher total WBC count
    • Possible Yu-Zhi (YZ) constitution
    • Odor perception for β-ionone

    Neurodegenerative Disease

    • Prediction of enhanced hippocampal volume
    • APOE E3/E3 genotype
    • Probably APOE E2/E4 genotype, Possibly E1/E3
    • APOE E2/E4 Genotype
    • APOE E4/E4 genotype
    • APOE E4/- genotype
    • APOE E3/E4 genotype
    • Bi-carrier of the minor alleles of rs1049296 and rs1800562
    • APOE E1/E1 Genotype
    • APOE E2/E2 Genotype
    • APOE E2/E3 Genotype
    • GAB2 rs2373115 (CC) and rs1800562 with APOE E4
    • GAB2 rs75932628(TT) Substitution
    • One short form 5-HTTLPR
    • Two long form 5-HTTLPR
    • Increased risk of Parkinson’s Disease
    • Decreased risk of Parkinson’s Disease
    • Increased risk of Parkinson’s Disease
    • Risk of autism related syndrome
    • Risk of autism related syndrome
    • Increased risk of autism/ social communication issues
    • Risk of autism related syndrome
    • Risk of autism related syndrome
    • Increased risk of Alzheimer’s Disease
    • Decreased risk of Alzheimer’s disease
    • Early-onset Alzheimer’s Disease risk
    • Elevated brain and cerebrospinal fluid concentrations of kynurenic acid
    • Lower levels of Indoleamine 2,3-dioxygenase (IDO1) activity

    Mind/ Body

    • Dopamine beta hydroxylase levels
    • Heightened placebo effect
    • Oxytocin ‘loner/ social empath’ polymorphism
    • Decreased risk of Alzheimer’s disease
    • Increased risk of bipolar disorder
    • Impaired motor skills learning
    • Increased risk of high cortisol levels when under stress
    • Lower levels of platelet MAO
    • D2 receptor DRD2 A1/A2 polymorphism
    • For Hispanics, 9 times more likely to develop heroin addiction ; risk of bi-polar issues
    • Increased risk for panic disorder (1.7x more likely)
    • Risk and intensity of functional somatic syndromes (CFS, FM)
    • Normal pain sensitivity
    • Variance in ‘self-referential’ processing in the brain
    • Higher ‘g’ score (general cognitive ability)
    • Increased ‘process reward’ from staring at smiling faces

    Methylation

    • MTHFR Polymorphisms Affecting Enzyme Activity
    • Risk of asthma, ADHD and Parkinson’s disease from high histamine
    • Epistatic subtle variants in COMT activity and pain sensitivity
    • Higher B12 Levels
    • Approximately​ 50% reduction ​in tetrahydrobiopterin (BH4) production and total biopterins
    • Risk of methyl trapping from high-dose/ premature methylation supplementation

    Auto-Immune/ Inflammatory

    • ‘Outside-in’ versus ‘inside-out’ genesis of atopic dermatitis.
    • Significant autoimmune disorder risk (HLA-DRA)
    • Moderate autoimmune disorder risk (HLA-DRA)
    • Increase risk of rheumatoid arthritis
    • Decreased soluble adhesion factors
    • Risk of autoimmune disorder/ gluten sensitivity
    • Risk of autoimmune disorder/ gluten sensitivity
    • Lower disorder/ gluten sensitivity risk (HLA-DQA1)
    • C-Reactive Protein Genotypes, Nutritional Status and Inflammation
    • Increased risk of allergic asthma
    • HLA genotypes and haplotypes
    • Increased risk of Crohn’s disease
    • Reduced risk (0.26) of Crohn’s disease and ulcerative colitis
    • Risk of Crohn’s disease
    • Increased risk of cluster headaches
    • Increased risk of migraine without aura
    • Increased headache frequency/use of analgesics medication
    • Increased risk of several autoimmune diseases
    • Increased risk of chronic fatigue syndrome
    • Slightly higher risk (1.17) of atopic dermatitis
    • Normal susceptibility to development of childhood asthma
    • Significantly increased risk several autoimmune diseases
    • Increased risk of rheumatoid arthritis

    Diet and Lifestyle

    • Effects of TP53/ high fat diet on Type 2 diabetes and obesity
    • Any type of exercise results in weight loss
    • High energy exercise required for weight loss
    • Balanced diet works best
    • Benefits from low-fat diet
    • Problematic effects from high fat diet
    • Benefits from low-carb diet
    • Novelty-seeking behavior
    • Possible high pain sensitivity
    • Possible low pain sensitivity
    • CYP1A2 ‘slow metabolizer’ Caffeine sensitivity
    • Ethanol biodisposition
    • Slower response to the effects of alcohol
    • Normal/increased rate of aging, reduced risk of dementia
    • Increased risk of nicotine addiction/ depression and loneliness in men
    • Sun sensitivity: No freckles and tans

    Digestion

    • Increased risk of diarrhea-predominant irritable bowel syndrome in women
    • Increased risk of diarrhea-predominant irritable bowel syndrome
    • Blood group B non-secretor: Increased risk of pancreatitis and high lipase levels

    Female Health

    • 10x higher risk for endometriosis, 0.5x lower risk for endometrial cancer, 0.76x less cognitive impairment with age
    • Evidence of earlier onset of menarche/ breast development
    • Decreased risk of hypertensive disorder complicating pregnancy

    Male Health

    • Severe risk of testicular germ cell tumors
    • Significantly increased risk of male pattern baldness

    Aging Related

    • Multi-gene Evidence of Longevity
    • 30-40% increase in MnSOD activity in mitochondria
    • Age related macular degeneration
    • AMD/ antioxidant response genotype group 1
    • Increased risk of developing osteoarthritis
    • Bone mineral density
    • Reduced memory abilities
    • Effect of FOXO3 and CFH polymorphisms on longevity
    • Possibly increased longevity; increased risk of colorectal cancer
    • Increased lifespan, better response to chemotherapy
    • Significantly younger, healthier kidney function
    • No increased likelihood of Fuchs’ dystrophy

    Endocrine Related

    • Possible corticosteroid resistance/ high cortisol syndrome
    • SHBG Levels affecting serum testosterone

    Hereditary Metabolic

    • Serum vitamin D levels
    • Increased risk of elevated uric acid levels and gout
    • Hereditary Hemochromatosis
    • Increased risk of Alpha-1 Antitrypsin Deficiency
    • Lower levels of tetrahydrobiopterin
    • Reduced conversion of beta-carotene to retinol
    • Low carotenoid conversion/ Low macular pigment optical density
    • Probably lactose tolerant
    • Probably lactose intolerant
    • Significantly Increased risk of Type II Diabetes
    • Lower circulating levels of adiponectin
    • Single HLA-DQ8 haplotype: Significant risk of Type I Diabetes
    • Mild trimethylaminuria
    • Increased hypersensitivity response to non-steroidal anti-inflammatory drugs
    • Reduced obesity and type 2 diabetes risk
    • Increased risk of metabolic syndrome/ consequences
    • Lowered risk of obesity
    • Increase risk of obesity
    • Wet earwax/ normal body odor/ normal colostrum
    • Increased risk (1.74) of gout
    • Significantly lower arachidonic acid and linoleic acid levels and higher interleukin (IL)-6 levels
    • Increased risk of T2DM from decreased capacity to scavenge ROS
    • Increased risk of elevated uric acid levels and gout
    • Increased risk of primary biliary cirrhosis
    • Lower serum levels of vitamin B12
    • Higher serum levels of vitamin B12
    • Lower serum levels of magnesium

    Resistance/ Immunity

    • Increased risk of Candida carriage
    • Increased risk of human papillomavirus persistence
    • Resistance to Norwalk norovirus infection
    • Increased risk of heightened inflammatory response/ antibiotic-refractory Lyme arthritis

    Musculo-skeletal

    • Training spectrum and traits indicative of elite athlete status
    • Increased musculoskeletal pain from fibromyalgia and temporomandibular disorders
    • Lower risk of lumbar disc disease
    • Increased risk of muscle cramps upon exertion

    Cardiology

    • Risk of venous thromboembolism
    • Lower heart attack risk (59%) than average
    • Decreased blood pressure levels
    • 300% increased risk of venous thrombosis
    • Lower risk (35%) of a heart attack or cardiovascular incident
    • Risk of myocardial infarction
    • Increased risk of Atrial Fibrillation
    • Risk of myocardial infarction and aspirin resistance
    • Higher blood viscosity potential
    • Ratios of TC/HDL and LDL/HDL probably benefit from skimmed milk
    • Lower HDL levels
    • Celera GRS: Reduced risk of coronary artery disease.
    • Increased risk of hypertension, but better response to therapy
    • Decreased risk (0.78) of heart attack
    • Aneurysms, both brain and abdominal aortic
    • Risk of salt-sensitive hypertension
    • Ten fold higher risk for heart disease in hereditary hemochromatosis patients with SOD2 mutation

    Oncology

    • Adiponectin intermediate signaler
    • Increased risk of ER+ breast cancer
    • Significantly increased risk of breast cancer
    • Adiponectin low signaler
    • Progesterone receptor gene PROGINS haplotype
    • Evidence of decreased risk of ovarian cancer
    • Increased risk of thyroid cancer
    • Increased risk of skin cancer
    • Decreased risk of skin cancer
    • Significantly increased risk of prostate cancer
    • Increased risk of prostate cancer
    • Increased risk of prostate cancer
    • Increased susceptibility and worsened outcome in malignant melanoma
    • Increased surveillance for colorectal cancer recommended
    • Lower risk of oral and upper digestive cancer
    • Risk hereditary Breast/ Ovarian / Prostate Cancer Syndrome
    • Increased risk of various types of cancer
    • Increased risk of colorectal cancer
    • Decreased risk of “upper aerodigestive” cancers
    • Substantially increased odds of developing V617F-positive MPN
    • Slightly increased risk of colon cancer
    • Increased risk of rectal bleeding after radiation therapy for prostate cancer
    • Increased risk of ‘chemobrain’

    Detoxification

    • CYP2D6*8 double reduced metabolism
    • CYP2C9 poor metabolizer
    • Pseudocholinesterase deficiency
    • CYP2D6*7 double reduced metabolism
    • CYP2D6*41 decreased metabolism
    • CYP3A5 non-expressor
    • CYP2C19 Extensive or Ultra-Fast Metabolizer
    • CYP2D6*6A reduced metabolism
    • CYP2D6*6A poor metabolizer
    • CYP1A2 fast metabolizer
    • CYP2D6*8 reduced metabolism
    • CYP2D6*8 poor metabolizer
    • CYP2D6*10 reduced metabolism
    • CYP2D6*10 poor metabolizer
    • CYP2D6*9 double reduced metabolism
    • CYP2D6*2 normal metabolism
    • CYP2C9 Intermediate Metabolizer
    • NAT2 Slow Metabolizer
    • NAT2 Intermediate Metabolizer
    • NAT2 Rapid Metabolizer
    • CYP2C19 normal/rapid metabolizer
    • CYP2D6*39 Normal Metabolizer
    • Possible CYP3A5 non-expressor
    • GSTM1 ‘Null’ Genotype

    Pharmacogenomics

    • Preferred form(s) of B12 supplementation
    • Adverse response to inhalers (Advair, Ventolin, Albuterol)
    • Decreased response to chemotherapy
    • Lower chemoresistance to anticancer drugs mitoxantrone, methotrexate, doxorubicin and camptothecin-based anticancer drugs
    • Adverse response to chemotherapy [neutropenia/leucopenia] from 5-fluorouracil
    • Increased chemoresistance to anticancer drugs mitoxantrone, methotrexate, doxorubicin and camptothecin-based anticancer drugs
    • Breast cancer chemotherapy: risk of hematological and gastrointestinal toxicities
    • Gefinitib takers more susceptible (4.0) to diarrhea
    • Increased toxicity to methotrexate
    • Gastric cancer: better response to chemotherapy
    • Increased risk of toxicity in cancer patients receiving 5-fluorouracil chemotherapy
    • Poor warfarin metabolizer
    • Intermediate warfarin metabolizer
    • Abnormal statin metabolizer
    • Favorable response to statin therapy likely
    • Impaired NSAID drug metabolism
    • No benefit from bupropion treatment for smoking cessation
    • Poor metabolism of proton pump inhibitor drugs
    • Poor metabolism/ adverse effects risk from clopidogrel (Plavix)
    • Less benefit from cyclophosphamide therapy in breast cancer

    Algorithms are added to Opus 23 fairly regularly and we suspect this will continue well into the future.

    “An algorithm must be seen to be believed.” –Donald Knuth

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  • Decoding 23andMe ‘i’ Numbers

    23andMe currently reports over 600,000 SNPs in the genome explorer, which are analyzed by their custom 2014 v4 chip. The process used is genotyping, rather than sequencing. The former is cheaper and quicker, and targets specific parts of the genome that are known to have variants in some or many people; the latter is used to find out the code of nucleotide base pairs in a sequence (or continuous stretch) of DNA, the exome (the coding part of DNA), or all the DNA in the whole genome.

    Genotyping does not report on all possible insertions or deletions. In general, it only reports small changes, spanning only one or a few bases. Sequencing will check whether all the DNA code in a region is found in the usual configuration or whether there are any unknown insertions or deletions.

    23andMe doesn’t test for all the SNPs they report on, but might impute variants present on larger chips or in sequencing analysis, using a statistical method that allows researchers to fill in missing data. This may be the reason 23andMe say “This data has undergone a general quality review, however only a subset of markers have been individually validated for accuracy.” [1]

    An example of this might be RhD blood group status: If you have a double deletion (DD) at “i4001527” you are RhD negative, if you don’t have the double deletion (DI or II) you are Rh positive. This number is available from a search in the 23andMe explorer, but is not found in the raw data can be downloaded in an ASCII text file and used for uploading to Opus23 Pro.

    Most of the numbers representing SNPs in the 23andMe raw data begin with ‘rs’, which are reference SNP identifiers, or reference SNP cluster IDs. [2] These rsIDs are assigned and managed by dbSNP, the official database for short genetic variations. However some numbers in the 23andMe raw data begin with ‘i’, which is an internal number assigned by 23andMe for testing locations on the genome for various reasons. This includes SNPs where the probes used differ from the reference sequence.[3] Some ‘i’ numbers are SNPs that don’t have rsIDs: 23andMe maps the i-number to the chromosome position, and internally they map this number to anything else they need to know about the SNPs to put it on a chip (many of these SNPs come from the custom portion of the genotyping array). Other ‘i’ numbers relate to SNPs that could highlight a genetic mutation in a user which is related to significant health risks or genetic conditions. The FDA don’t want users to be able to find out that they have these problems without genetic counselling, except for under specific circumstances where the user has made a declaration that they understand the consequences of accessing this data and what it might mean. The FDA are currently seeking medical opinion on situations where genetic test results might be available directly to the user. Comments can be submitted online  to the FDA by March 31st 2016. All submissions must include reference to: “Docket No.  FDA-2015-N-4809 for `Patient and Medical Professional Perspectives on the Return of Genetic Test Results; Public Workshop; Request for Comments.’”

    How does Opus23 Pro deal with ‘i’ numbers?

    Opus23 Pro curators use the genomic location linked with the coded ‘i’ numbers to find the rsID (if one exists), and if relevant, the ‘i’ numbers are added to the Opus23 Pro SNP database, and a lookup is performed by the software when analysing a client’s raw data. The ‘i’ numbers are linked with the rsID in the software, and this gives the practitioner a reference for further research in published medical literature. Any significant genetic risk factors can be added to the client report and explained to the patient, along with genetic counselling as necessary.

    References:

    1. Web page: “How 23andMe Reports Genotypes” https://customercare.23andme.com/hc/en-us/articles/212883677-How-23andMe-Reports-Genotypes.  Accessed 3/5/16
    2. The NCBI Handbook [Internet]. 2nd edition. Bethesda (MD): National Center for Biotechnology Information (US); 2013-. Accessed 3/5/16

    3. 23andMe forum “23andMe upgrading to NCBI Build 37 coordinates on Aug. 1” https://www.23andme.com/you/community/thread/14308/6/ Accessed 3/5/16
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  • SuperMogadon

    SuperMogadon is a highly flexible search and sort tool that allows you to easily compare the client’s genotype with results from Genome Wide Association Studies* (GWAS) through the Opus 23 Pro database.

    As you can see there are over 50+ pages of GWAS data in SuperMogadon, which would make grinding through the data rather impractical. Like most data displays in Opus 23 that deal with large amounts of data, SuperMogadon features a ‘filterable’ display. Type full or partial search terms into the search box at the upper left hand corner and SuperMogadon immediately displays only those results.

    Click on the graph icon to display SNP distribution for that pathology or trait as a Manhattan Plot. Click on any column title to sort by that column.

    SuperMogadon Index Page
    SuperMogadon Index Page

    Clicking on the blue graph icon in the ‘Show Plot’ column will launch the SuperMogadon Manhattan plotter for that disease/trait.

    TheSuperMogadon Viewer is a GWAS Manhattan plotter, a type of scatter chart used to display data with a large number of data-points. Genomic SNP coordinates (marked by chromosome) are displayed along the X-axis, with the negative logarithm of association P-value for the disease or pathology displayed on the Y-axis. Because the strongest associations have the smallest P-values (e.g., 10 −15), their negative logarithms will be the greatest (e.g., 15). In the example above, we see the graph for ‘Type II diabetes’ as a GWAS Manhattan plot.

    Client SNP genotypes results are shape and color-coded:

    • Gray-colored points denote client SNPs that do not contain the risk allele
    • Orange-colored points denote that the client is homozygous for the risk allele
    • Yellow-colored points denote that the client is heterozygous for the risk allele
    • Square-shaped points signify that the SNP is in the GWAS and Opus 23 Pro databases and when clicked will trigger an information pop-up
    • Circle-shaped points signify that the SNP is not in the Opus 23 Pro database but is in the GWAS database and is reported by 23andMe. When clicked these SNPs will bring up its GWAS PubMed reference article

    Drag-select to zoom section or use the scroller at the bottom. Hover over any point to learn more. Clicking on any point triggers a full-information popup window. Like any other element in Opus 23 Pro, you can notate the SNP in SuperMogadon Viewer by clicking on the link to bring up the information pop-up, then clicking the ‘Add/Edit Note’ button at the top of the pop-up screen. You can also send any popup element directly to curation (so that it shows up in the Client Report.)

    Opus 23 Pro subscribes to the philosophy of ‘TMTOWTDI’ (There’s more than one way to do it, pronounced ‘Tim Toady’.) The program was designed with this idea in mind, in that it ‘doesn’t try to tell the physician how to parse the data.’ Rather, it presents many different frameworks and cross-sections of the available client data, using a myriad of infographic treatments. This (and our ability as a species to excel at pattern recognition) dramatically increases the odds that a noteworthy finding will not go undiscovered.


    * In genetic epidemiology, a genome-wide association study (GWA study, or GWAS), also known as whole genome association study (WGA study, or WGAS), is an examination of many common genetic variants in different individuals to see if any variant is associated with a trait. GWASs typically focus on associations between single-nucleotide polymorphisms (SNPs) and traits like major diseases.

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  • Protocol development

    Two years ago I developed a software app called SkySaw for use on my teaching shift at the COEGM. SkySaw allows clinicians to structure patient encounters as a linked network (technically a directed acyclic graph). What made this attractive was that these individual networks could be connected together into a great network. One could then use graphing tools to data-mine relationships, trends and outcomes.  As the first stage of Opus23 Pro moves to completion, I decided to port this app over to Opus.  What follows is the online doc file for PROTO, the Opus 23 app.

     

    PROTO allows you to develop a flow-chart (network) based approach to health protocol management. Creating a protocol network in PROTO is easy. Protocols can then be added to the client report, allowing for a more client-friendly way of relating your clinical decisions.

    Actions are classified by various roles you can assign any node:

    avatars

    Just choose and option from the menu at the top right-window:


    From left the right, the options are:

    • Reset the screen: Ticking this will reset the screen and zoom level. You can zoom in and out by using the scroll function of your mouse. You can move the network around by click-grabbing the network and moving your mouse.
    • Back to protocol dataset list: Ticking this will return you to the list of datasets for the various protocols you’ve created
    • Add a new node (plus sign): Ticking this will launch a popup window that allows you to add a new node to the network. You then give the node a name and a type (food, drug, molecular target, lab test, etc.) and if you wish provide a short bit of accompanying text.
    • Add a new edge (two connected nodes): Ticking this will launch a popup window that allows you to add a new edge to the network. Edges connect nodes. The input fields will autosuggest nodes to use based on the existing nodes in the network.
    • Info screen: Ticking this will launch this popup window.
    • Active dataset indicator: This icon shows if the protocol you are working on is the active dataset (i.e this is the protocol that will go on to be included in the client report, if you desire.)

    Editing nodes and edges: You can edit any node of edge in the map by clicking on it. This will launch the appropriate popup that will be populated with the existing data. You can make any changes and then save.

    Map direction: The map is designed to proceed in its development from left to right.

    Adding nodes on the fly: Certain node types (molecular targets, agents and foods) can be added from their own information popups. For example, clicking on any gene symbol in Opus 23 Pro launches the gene information popup for that gene. Clicking on the ‘add to protocol’ icon


    will add that gene to the current protocol as a ‘molecular target’ node.

     

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  • Client-friendly reporting

    I designed Opus 23 Pro to serve two user audiences: the physician who works in the development environment to generate and curate information; and the client, who represents the end-user of that information. Both have widely differing needs and points of reference. One aspect of Opus 23 Pro that I am especially proud of is the great lengths the program goes to to make its final product (the Client Report) simple, concise and easy to understand. One area that has an especially interesting and dynamic quality is the way that Opus 23 explains the actions and consequences of genes to the client.

    Opus 23 Pro aggregates much of its data from public, peer-reviewed sources. This includes the descriptive text that accompanies information about genes. Typically Opus 23 grabs this information from genome.gov. However these short abstracts are often highly technical and cryptic -very unlikely to be very helpful to a patient who does not have a background in genetics. So we created an alternate database of gene descriptions specifically written for the layperson, which is used when Opus 23 Pro generates the client report.

    However, even simplified gene descriptions can be somewhat technical and often rely on the reader having some form of base knowledge.

    Here is a nice touch you don’t see very often. When Opus prints out the gene description in the client report it checks its internal glossary for any advanced medical concepts and if they are in the description the ‘smart owl’ will activate and give the client a simple description of the term.

    csf

    To avoid repeating itself endlessly, Opus only adds the glossary description to the first description that requires it. In this screen shot it is explaining what the terms ‘gene,’  ‘interleukin,’ cytokine and ‘protein’ mean.

     

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