User:Seppi333

Reliability of Wikipedia Amusing comics about an issue I routinely face when writing Wikipedia: overly technical vs overly simplistic

I'm a statistician, bioinformatician, and the chief executive officer of a precision medicine startup company with 5 corporate officers and 1 full-time employee that is incorporated under the name PathoGene. I have three bachelor's degrees in mathematics, finance, and economics from UMD College Park and I studied for 2 years in UNC Chapel Hill's Interdisciplinary Statistics and Operations Research PhD program. In a less formal or non-academic setting, I have also studied and taught bioinformatics and artificial intelligence – specifically, machine learning and natural language processing – with a focus on implementations in Python 3. An example of this on Wikipedia is my data pipeline from the HGNC database to the article space that algorithmically edits the list of human protein-coding genes articles through my bot account:  Seppi 333 Bot.

I've been a Wikipedia editor since May 2013 (NB: my all time editing history statistics are |namespace-totals|year-counts|month-counts|top-edited-pages shown here). I was born in Washington D.C., raised in Potomac, Maryland, and currently live in Los Angeles, California.

In addition to the aforementioned subject areas, I have a general interest in and broad knowledge (via autodidactic learning) of molecular biology, cell biology, systems biology, pharmacology, medicine, immunology, physiology, psychology, and neuroscience; I have a rather deep understanding of very specific niches which lie at the intersections of these fields due to having read countless primary research and/or review articles on pertinent topics and usually written extensively about on Wikipedia; specific niches of interest to me include pathophysiology, cognitive neuropsychology, neuroepigenetics, systems neuroscience, neuroimmunology, immunopharmacology, molecular neuropharmacology, multi-omics (particularly genomics, toxicogenomics, metagenomics, metatranscriptomics, pharmacomicrobiomics, and metabolomics), molecular diagnostics, and precision medicine. I typically only edit articles on topics within the scope of one or more of the aforementioned biomedical subject areas, statistics, econometrics, artificial intelligence, and/or bioinformatics.

My primary goal as an editor is to improve the accuracy and overall quality of the health information on Wikipedia; hence, I tend to spend most of my editing time on article content creation and revision (exopedianism), but frequently contribute in other areas of Wikipedia and other Wikimedia content projects (mainly and ). I also spend a fair amount of time wikignoming and regularly donate 2¢ to several WikiProjects – specifically, WT:MED, WT:NEURO, WT:MCB, and WT:PHARM – because I'm very generous with my pocket change.

Editing statistics

 * |namespace-totals|year-counts|month-counts|top-edited-pages My edit history statistics – includes my general editing statistics (e.g., monthly/yearly and cumulative edit counts), a list of pages I've edited the most, and a breakdown of my edits by namespace.
 * List of the top 1000 articles I've edited, ranked by my edit count
 * List of all templates that I've edited, ranked by my edit count
 * List of all articles that I've created and list of all article redirects that I've created (934 total pages: 34 articles and 900 redirects as of January 2019)

How I've contributed
Some of my most notable contributions to Wikipedia: This list includes articles in which I've written >80% of the source code (according to xTools' authorship attribution for the article) and for which I've spent the most time locating, reading, and citing WP:MEDRS-quality sources. These pages contain a complete list of all known human protein-coding genes. I've been using a Python algorithm to regularly rewrite/update them.
 * Articles:
 * Amphetamine (Page statistics) – became a featured article in January 2015
 * Also: Adderall (most of this article's source is transcluded from the amphetamine article) – became a good article in December 2014
 * β-Hydroxy β-methylbutyric acid (Page statistics) – became a featured article in March 2018
 * Neurobiological effects of physical exercise (Page statistics) – this article is still a work in progress
 * Lists:
 * List of human protein-coding genes 1
 * List of human protein-coding genes 2
 * List of human protein-coding genes 3
 * List of human protein-coding genes 4
 * Templates:
 * The image annotation template that I coded for overlaying wikitext onto diagrams:
 * Annotated image 4
 * Examples of technical images I've drawn and annotated with wikitext markup:
 * Annotated image: – image file: File:ΔFosB.svg
 * Annotated image: Catecholamine and trace amine biosynthesis – image file: File:Catecholamine and trace amine biosynthesis.png
 * Annotated image: Amphetamine pharmacodynamics – image file: File:TAAR1 Dopamine.svg
 * Annotated image: Leucine metabolism in humans – image file: File:HMB biosynthesis and metabolism diagram - no labels.svg
 * Annotated image: Estradiol metabolism – image file: File:Estradiol metabolism.svg
 * Annotated image: Tryptophan metabolism by human microbiota – base image file drawn by another user

For myself
Web shell login page: PAWS

Who qualifies to be a bioinformatician?

Cross-wiki userpage links
Links to my userpages on other Wikimedia projects where I contribute content:
 * Commons userpage – Commons:User:Seppi333
 * Wiktionary userpage – Wikt:User:Seppi333
 * Wikidata userpage – Wikidata:User:Seppi333
 * Meta-Wiki userpage – Meta:User:Seppi333
 * Chinese-Wikipedia – zh:User:Seppi333 (I mainly assist with porting my contributions in articles/templates over to this Wikipedia; I can't read/write Chinese)

John
Quick summary of findings from a few of the teams:
 * Undiagnosed-1 GitHub repository: https://github.com/SVAI/Undiagnosed-1
 * Multiple teams implicated TTN in the pathophysiology of John's clinical phenotype (see here for a list of TTN mutations).
 * Two teams implicated TNXB haploinsufficiency (technically, TNXB deficiency), manifesting as hypermobile Ehlers-Danlos syndrome, due to compound heterozygous frameshift mutations in this gene, both of which occur at tenascin-X glycine residue 362.
 * Several teams implicated genes associated with a congenital disorder of glycosylation; other genes related to lipid metabolism/storage, were also implicated in the etiology of his metabolic phenotype.
 * NB: I haven't yet looked into the genes implicated in the etiology of John's immunological phenotype, so I can't summarize this.

Partially penetrant TNXB deficiency
John's genotype: compound heterozygous frameshift mutations in TNXB per Team Tenasity's list of genes with suspectedly benign/tolerated or penetrant pathogenic mutations

The following symptoms that John experiences are associated with TNXB loss of function mutations: NB: complete TNXB deficiency normally causes classic-like EDS and manifests with a much more pronounced phenotype than what John experiences; his clinical phenotype is much more similar to hypermobile EDS, most notably due to an apparently complete lack of skin involvement, so it would seem that John's genotype is not fully penetrant for clEDS.
 * joint hypermobility
 * joint subluxation (partial joint dislocation)
 * spinal disc herniation (i.e., slippage/dislocation) (per )
 * some spinal disc dessication (per same ref)
 * joint/muscle pain (per this ref)
 * muscle weakness (per this ref)
 * muscle hypotonia - low muscle tone (per this ref)
 * easily fatigued
 * Gastrointestinal and vomiting reflex arc symptoms
 * gastrointestinal dysmotility
 * visceral/gastric hypersensitivity
 * stomach pain
 * gastric distension
 * hiatal herniation
 * heartburn
 * gastroesophageal reflux
 * nausea/vomiting (A novel role for the extracellular matrix glycoprotein-Tenascin-X in gastric function: covers the involvement of tenascin-X in vagal reflexes like nausea/vomiting and the aforementioned GI symptoms)
 * Other (biomarker abnormalities)
 * elevated plasma histamine (likely reflects the involvement of mast cell disorders in EDS per )

Hackathon teams that identified the biallelic frameshift variants in his TNXB gene: Genobank & Tenacity (PPT) – both found it with Qiagen's proprietary Ingenuity Variant Analysis software.

Relevant studies
PubMed search link for ("TNXB"[Title/abstract] OR "tenascin-X"[Title/abstract] OR "tenascin X"[Title/abstract]) AND ("EDS"[Title/abstract] OR "Ehlers-Danlos syndrome"[Title/abstract] OR "joint hypermobility"[Title/abstract])


 * Primary study (2003): Haploinsufficiency of TNXB Is Associated with Hypermobility Type of Ehlers-Danlos Syndrome "Clinically, patients with reduced TNX levels showed hypermobile joints, often associated with joint subluxations and chronic musculoskeletal pain (table 1). The clinical findings in these patients differ from those with complete TNX deficiency. Patients with haploinsufficiency do not have skin hyperextensibility and lack the easy bruising seen in patients with TNX deficiency. In addition, TNXB haploinsufficiency is expected to be an autosomal dominant trait, which is in accordance with the observed mode of inheritance of HT-EDS and BJHS."
 * Review (2017): Hypermobile Ehlers–Danlos Syndrome (a.k.a. Ehlers–Danlos Syndrome Type III and Ehlers–Danlos Syndrome Hypermobility Type): Clinical Description and Natural History; hEDS also includes anxiety and chronic fatigue in its clinical description, but the genetic basis for hEDS is not limited to TNXB. Moreover "the exact physiologic process remains unknown and heterozygous tenascin-X deficiency accounts for only a small percentage of hEDS." TNXB haploinsufficiency has only partial penetrance for hEDS per this review.
 * Primary study (2013): Tenascin-X Haploinsufficiency Associated with Ehlers-Danlos Syndrome in Patients with Congenital Adrenal Hyperplasia (NB: the TNXB gene overlaps the CYP21A2 gene at its 3' ends; this paper is about mutations which affect both TNXB/CYP21A2, resulting in CAH & EDS) "Twelve of 13 patients with CAH-X had EDS clinical features. Patients with CAH-X were more likely than age-matched controls to have joint hypermobility (P < .001), chronic joint pain (P = .003), multiple joint dislocations (P = .004), a structural cardiac valve abnormality by echocardiography (P = .02), and reduced tenascin-X expression by Western blot and immunostaining. A subset of parents had clinical findings. → high penetrance of haploinsufficiency
 * Case Report (2016): Mutation in TNXB gene causes moderate to severe Ehlers-Danlos syndrome
 * Primary study (2019): Measurement of Serum Tenascin-X in Joint Hypermobility Syndrome Patients "In conclusion, we found out that sTNX concentrations in half of the 17 JHS/hEDS patients were significantly lower than those in healthy individuals and there were no mutations, insertions or deletions in TNXB except for one patient. At present, the reason for reduction in sTNX concentration without mutations of TNXB is not clear, but the expression of TNX might be affected by epigenetic changes that occur in the JHS/hEDS patients. Therefore, the results indicate that measurement of the sTNX concentration in patients with JHS/hEDS is beneficial and the decrease in sTNX concentration could be used as a risk factor for JHS/hEDS." – might be worth getting a TNXB ELISA if the antibody can actually bind to John’s mutant tenascin-X proteins, but altered protein function needs to be considered.
 * Review (2018): Tenascin-X, Congenital Adrenal Hyperplasia, and the CAH-X Syndrome. "Rarely, patients with severe, salt-wasting CAH have deletions of CYP21A2 that extend into TNXB, resulting in a "contiguous gene syndrome" consisting of CAH and EDS. Heterozygosity for TNXB mutations causing haploinsufficiency of TNX may be associated with the mild "hypermobility form" of EDS, which principally affects small and large joints. Studies of patients with salt-wasting CAH found that up to 10% had clinical features of EDS, associated joint hypermobility, haploinsufficiency of TNX and heterozygosity for TNXB mutations, now called 'CAH-X.'"
 * Primary study (2016): Ehlers-Danlos Syndrome Caused by Biallelic TNXB Variants in Patients with Congenital Adrenal Hyperplasia "Hypermobility type EDS is the mildest EDS subtype with generalized joint hypermobility, recurrent joint dislocations and chronic arthralgias can occur, and mild skin manifestations such as smooth, velvety skin may also be present. The genetic etiology of hypermobility type EDS is largely unknown (De Paepe and Malfait, 2012; Sobey, 2014). In this report, we describe a subtype of EDS in CAH patients with biallelic TNXB variants that clinically resembles the classical type EDS phenotype. Prior studies of patients with CAH and monoallelic TNXB variants reported a phenotype similar to the hypermobility type EDS (Merke, et al., 2013; Morissette, et al., 2015). ... This study describes a biallelic form of CAH-X syndrome that is clinically and biochemically more severe than the monoallelic forms previously described (Merke, et al., 2013; Morissette, et al., 2015). We have chosen to use the terminology “biallelic”, rather than “autosomal recessive” to describe our CAH patients with TNXB variants on both alleles because the term “autosomal recessive” by definition implies that having a deleterious variant on one allele does not result in a clinical phenotype. Clearly this is not the case with CAH-X. Similarly, biallelic variants of well-established autosomal dominant disorders resulting in a more severe phenotype have been described in polycystic kidney disease (Bergmann, et al., 2011; Hopp, et al., 2012; Sandford, 2009), familial hypercholesterolemia (Varret, et al., 2008) and inherited cancers (Rahman and Scott, 2007). Thus, our findings reflect complex genetic heterogeneity not unexpected. ... However, the development of in vitro constructs for probing variants in TNX and the effect on its mechanism of action would provide useful functional information."

Given what the Ehlers-Danlos society has written about the association between TNXB haploinsufficieny and hypermobile EDS as well as TNXB deficiency and classical-like EDS − and that John's clinical phenotype is more characteristic of hEDS diagnosis while his genotype is diagnostic for clEDS due to complete TNXB deficiency − this actually seems more of a research issue than a diagnostic one. Hence, have referred him to contact the EDS society directly for assistance with his case.  Seppi  333  (Insert 2¢) 03:27, 18 May 2020 (UTC)

Clinical metabolic phenotype
- pending admission, I'm just leaving this to the UDN; otherwise, I'll construct a customized GCP pipeline to do my own hybrid assembly, use a novel non-DeepVariant, AI-based variant caller, and then annotate the variants with both pre-existing software as well as my own NLP-based content similarity approach using an annotation database and the medical records textract files to do my own analysis. Then, will compare to Hackathon teams that focused their analysis on this subset of protein-coding genes.
 * 1) IIRC, ~2-3 genes associated with congenital disorders of glycosylation were repeatedly implicated by different teams for part of this phenotype.
 * 2) A second common theme involved peroxisomal disorders and/or lysosomal storage disorders, but I didn't look into those analyses in much detail.

Relevant clinical metabolic phenotype:
 * failure to thrive
 * physical fatigue (non-localized, possibly a manifestation of central nervous system fatigue rather than diffuse muscle fatigue )
 * inability to gain body fat or lean mass despite consuming sufficient calories (symptom is highly responsive to chronic benzodiazepine use, during which it largely resolves [i.e., results in a gain of ~10-20 pounds of body mass]; body weight eventually returns to an abnormally low baseline upon cessation of benzodiazepine use)
 * multiple abnormally high glycosylphosphatidylinositide (GPI-anchored) lipid biomarkers – metabolome profiling revealed over half a dozen GPI-anchored lipids with serum concentrations of ~3σs above their population means
 * ... [incomplete list]

Clinical immunological phenotype
- pending admission, I'm just leaving this to the UDN; otherwise, I'll see if I can augment the analyses from the hackathon with a hybrid nanopore/Illumina assembly and apply the suggested types of variant callers mentioned in the presentations.
 * 1) I don't have a working knowledge of immune defense against viral pathogens and only a basic understanding for fungal pathogens, so I haven't gone through these hackathon analyses.

Relevant clinical immunological phenotype:
 * recurrent plantar warts over a period of several years despite multiple cryosurgeries and treatments with topical acid solutions, which eventually resolved following HPV vaccination
 * frequent fungal skin infections when he was a teenager
 * chronic low-grade mucosal inflammation in multiple regions of the GI tract per various biopsies/endoscopies
 * ... [incomplete list]

External databases
Individual resources:
 * HGNC: Specialist resources
 * HGNC: Human Genome Databases and Browsers
 * HGNC: Protein resources
 * HUPO: Human Proteome Project Information Resources
 * HGNC: Bioinformatics Analysis Tools
 * GeneReviews – peer-reviewed disease descriptions
 * NCBI Gene
 * NCBI Reference Sequence

Articles or sections to read/assess later:
 * Data analysis
 * Data analysis
 * Statistical power


 * Markov switching multifractal - model of asset returns in financial econometrics that is compared to GARCH
 * Cox regression
 * Heckman correction

Topics to research later:
 * Universal portfolio algorithm (machine learning approach to portfolio selection for algorithmic trading; perhaps analogous to factor models?)

Articles/topics directly related to fundamental factor models:
 * Factor analysis (statistical framework)
 * Factor theory (financial framework)
 * Fundamentally based indexes (stock indexes based upon fundamental factor models)
 * Goldman Sachs asset management factor model (example of a fundamental factor model)
 * MSCI (example of an index based upon a fundamental factor model)

Statistics articles for self-reference

 * Lists
 * List of statistics articles
 * Notation in probability and statistics
 * List of probability distributions
 * Glossary of probability and statistics
 * List of graphical methods
 * List of fields of application of statistics


 * Bias-related
 * Heterogeneity in economics
 * Homogeneity (statistics)
 * Errors and residuals
 * Statistical hypothesis testing
 * Bias (statistics)
 * Bias of an estimator
 * Omitted-variable bias
 * Systematic bias
 * Observer bias
 * Selection bias
 * Attrition bias
 * Measurement error


 * Modeling-related concepts
 * Model selection
 * Stepwise regression – automated model selection
 * Machine learning – algorithm-driven modeling
 * Hyperparameter optimization
 * Model validation
 * Estimation theory
 * Identifiability
 * Bayesian econometrics
 * Structural break


 * Selected regression models and methods
 * Distributed lag model
 * Time-series regression
 * Vector autoregression (VAR)
 * Autoregressive–moving-average model (ARMA)
 * Autoregressive integrated moving average (ARIMA)
 * Autoregressive conditional heteroskedasticity (ARCH)
 * GARCH
 * Feasible generalized least squares (FGLS)
 * Generalized least squares (GLS)
 * Panel data analysis
 * Fixed effects
 * Random effects
 * Mixed model
 * First-difference estimator
 * Pooled least squares regression
 * Errors-in-variables models


 * Theoretical basis in mathematics
 * Statistical theory
 * Asymptotic theory (statistics)
 * Convergence of random variables
 * Convergence in probability
 * Convergence in distribution
 * Probability theory
 * Independence (probability theory)
 * Mathematical statistics
 * Central limit theorem
 * Law of large numbers

Four possible cases of stationarity and nonstationarity (with an I(1) unit root) for regressors and the error term (yt=α+βxt+μt). The time-series behavior of y is governed by the behavior of x and μ:
 * Unit roots

Medicine, pharmacology, neuroscience, and molecular/cell biology article alerts

 * Medical article alerts


 * Pharmacology article alerts


 * Neuroscience article alerts


 * Molecular and Cell Biology article alerts

Molecular neuropharmacology textbook

 * Graduate level, 2nd edition (2009)


 * Graduate level, 3rd edition (2015)

Econometrics textbooks

 * Undergraduate and master's level


 * Graduate level

Help page links for searching within Wikipedia

 * Help:Searching
 * Help:Searching

Project space links and syntax references
MOS and popular page links:


 * MOS links: MOS:MED MOS:PHARM MOS:MATH MOS:MCB MOS:RDR
 * RS links: WP:MEDRS WP:RS
 * Popular pages: Pharmacology articles Medicine articles MCB articles

Other project space links:


 * Help:Special page
 * WikiProject Academic Journals/Journals cited by Wikipedia
 * Special:Search/insource:"abc" (searching the source of all pages for abc)
 * Special:Search/J addict prefix:Wikipedia:WikiProject Academic Journals/Journals cited by Wikipedia (search the WikiProject Academic Journals/Journals cited by Wikipedia page and all subpages for the text "J addict")
 * COMMONS:COM:FPC
 * Template messages
 * WP:USETEMP
 * Template:done
 * CSD Page, Template:G7 & Template:U1
 * WikiProject Pharmacology/Index – Drugbox
 * WikiProject Chemicals/Index – Chembox
 * featured articles and good articles

Modules/Parser functions and templates
Modules/Parser functions:
 * MW:Help:Extension:ParserFunctions
 * – a foreach loop

Maintenance templates:
 *  – for excessively technical sections
 * – for WP:PEACOCK sections
 * – for WP:WEASEL sections
 * – for insufficient context in sections
 * or – Used after text without a reliable medical source. Generates:
 * or – Used after text with a questionable medical source. Generates:
 * or – Used after text that cites a primary source. Generates:
 * – Generates a CN tag with text span to highlight specific text that requires citations. Ex:  generates

Miscellanous templates:
 * pinggroup, noping, U, to
 * Icon
 * – prevents bot archiving of a talk page section

Redirect templates:
 * For redirects that result from a merge, use: (Template:Talk page of redirect shortcut)
 * Category parameters for Redr are listed in the navbox below:

Miscellaneous links and article content
Editor tools


 * 1) Edit history statistics
 * 2) Article contributor ranking

Amusing pages


 * File:Roflcopter.gif
 * Template:P - particularly
 * File:Bathrobecabalicon.png
 * WP:TROUT


 * PMID 26180194 – Primary research paper that used novel statistical methodology to assess the dose-dependent effects of amphetamine on PFC-dependent working memory function
 * Open access textbook from 2014: Neurobiology of body fluid homeostasis
 * Interesting B vitamin review (happens to mention trace amines)
 * Niacin in metabolic syndrome—review
 * Niacin in vascular calcification—review

Cognitive control deteriorates (poorer reasoning and problem solving, forgetting things, and impaired ability to exercise discipline and self-control) as a result of: Impaired cognitive control can produce symptoms of ADHD in adults who did not have the disorder as a child.
 * excessive stress
 * sadness/depression
 * social isolation/loneliness
 * poor health
 * lack of physical exercise/fitness

Cognitive control can be improved through:
 * regular aerobic exercise
 * frequent and repeated performance of sufficiently difficult executive function training tasks
 * low doses of certain pharmaceuticals  (e.g., amphetamine and methylphenidate;  and, possibly to a lesser degree, atomoxetine and desipramine )


 * Citations to read through later
 * - mentions the effects of long-term stimulant use on the cerebellum
 * Immune Responses to Non-Tumor Antigens in the Central Nervous System