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> vol. 103 no. 51

> Matthew A. Zapala, 1943019435, doi: 10.1073/pnas.0609333103

Multivariate regression analysis of distance


matrices for testing associations between gene
expression patterns and related variables
1. Matthew A. Zapala* and
2. Nicholas J. Schork*,,

Author Affiliations

1. *Biomedical Sciences Graduate Program and the Polymorphism Research Laboratory,


Department of Psychiatry, and
2. Division of Biostatistics, Department of Family and Preventive Medicine, Moores
UCSD Cancer Center, Center for Human Genetics and Genomics, and the California
Institute of Telecommunications and Information Technology, University of California
at San Diego, 9500 Gilman Drive, La Jolla, CA 92093

1. Communicated by Dennis A. Carson, University of California at San Diego School of Medicine, La Jolla, CA,
October 25, 2006 (received for review July 25, 2006)

1. Abstract

2. Full Text

3. Authors & Info

4. Figures

5. SI

6. Metrics

7. Related Content

8. PDF

Abstract
A fundamental step in the analysis of gene expression and other high-dimensional genomic data is
the calculation of the similarity or distance between pairs of individual samples in a study. If one has
collected N total samples and assayed the expression level of G genes on those samples, then an N
N similarity matrix can be formed that reflects the correlation or similarity of the samples with
respect to the expression values over the G genes. This matrix can then be examined for patterns
via standard data reduction and cluster analysis techniques. We consider an alternative to
conventional data reduction and cluster analyses of similarity matrices that is rooted in traditional
linear models. This analysis method allows predictor variables collected on the samples to be related
to variation in the pairwise similarity/distance values reflected in the matrix. The proposed
multivariate method avoids the need for reducing the dimensions of a similarity matrix, can be used
to assess relationships between the genes used to construct the matrix and additional information
collected on the samples under study, and can be used to analyze individual genes or groups of
genes identified in different ways. The technique can be used with any high-dimensional assay or
data type and is ideally suited for testing subsets of genes defined by their participation in a
biochemical pathway or other a priori grouping. We showcase the methodology using three
published gene expression data sets.

analysis of variance

high-dimensional data

Footnotes
To whom correspondence should be addressed. E-mail: nschork@ucsd.edu

Author contributions: M.A.Z. and N.J.S. designed research, performed research, analyzed
data, and wrote the paper.

The authors declare no conflict of interest.

This article contains supporting information online at


www.pnas.org/cgi/content/full/0609333103/DC1.

Received July 25, 2006.

2006 by The National Academy of Sciences of the USA


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distance matrix regression analysis ...

A model for seasonal changes in time series regression relationships ...


onlinelibrary.wiley.com/doi/10.1002/sim.4780121704/pdf
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seasonal trends in time series regression relationships in the presence of ... affective
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Multivariate distance-based matrix regression (MDMR)... - Scientific ...


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See figure: 'Figure 1: Multivariate distance-based matrix regression (MDMR). ... Full-
text Article Aug 2014 The British journal of psychiatry: the journal of mental ...

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https://leftbrainrightbrain.co.uk/2009/09/24/fever-plus-mitochondrial-disease-could-be-risk-factors-for-
autistic-regression/

Definitions for regression(noun)(psychiatry) a defense mechanism in which you flee from reality by
assuming a more infantile state
Fever Plus Mitochondrial Disease Could Be
Risk Factors for Autistic Regression
24Sep

Autism, regression, mitochondrial disease and vaccines. With a combination like that, this paper
is likely going to be very important.

Fever Plus Mitochondrial Disease Could Be Risk Factors for Autistic Regression

Here is the abstract:

Autistic spectrum disorders encompass etiologically heterogeneous persons, with many genetic
causes. A subgroup of these individuals has mitochondrial disease. Because a variety of
metabolic disorders, including mitochondrial disease show regression with fever, a retrospective
chart review was performed and identified 28 patients who met diagnostic criteria for autistic
spectrum disorders and mitochondrial disease. Autistic regression occurred in 60.7% (17 of 28),
a statistically significant increase over the general autistic spectrum disorder population (P < .
0001). Of the 17 individuals with autistic regression, 70.6% (12 of 17) regressed with fever and
29.4% (5 of 17) regressed without identifiable linkage to fever or vaccinations. None showed
regression with vaccination unless a febrile response was present. Although the study is small, a
subgroup of patients with mitochondrial disease may be at risk of autistic regression with fever.
Although recommended vaccinations schedules are appropriate in mitochondrial disease, fever
management appears important for decreasing regression risk.

The authors note neurologic regression in general (not just autistic regression) is observed with
patients who have metabolic diseases:

Patients with mitochondrial diseases, like many patients with metabolic diseases, are at increased
risk of neurologic regression in conjunction with stressors such as fever, infection, and
dehydration.

They studied 28 patients who met DSM-IV criteria for autism and diagnostic criteria for
mitochondrial disease.

They define regression and whether it is related to fever thusly:

Autistic regression was defined as loss of developmental skills that included speech, receptive
skills, eye contact, and social interests in individuals years of age. A relationship between

fever and autistic regression is defined as regression beginning within 2 weeks of a febrile
episode without the suggestion of infectious meningitis or encephalitis.
One commentthe definition of regression is somewhat vague to me. What is also critically
important in this discussion is whether there were any signs of autism before the regression. Or,
as some may put it, is this regression into autism or autistics undergoing regression? Is there a
mix of pathways?

They state that 17 of the 28 patients studied underwent an autistic regression. This is higher than
the roughly 25% value for autistic regression they assumed for the general autism population,
and statistically significant.

In other words, they are saying that autistic regression may occur more often with kids with
mitochondrial diseases.

They note that some of the fevers could be linked to vaccination:

The 17 individuals with autistic regression could be divided into 2 groups, those who regressed
with fever (70.6%, 12 of 17) and those who regressed without identifiable linkage to fever or
vaccinations (29.4%, 5 of 17).

And,

No individual showed regression with vaccination unless a febrile response was present.

They discuss the concerns with vaccination in the conclusion, noting that vaccination is still
recommended for children with mitochondrial diseases. My experience in discussing this issue
with mitochondrial disease experts is that they find vaccination to be extremely important. If, for
some reason, they decide to not vaccinate a child with mitochondrial disease, they insure that all
family members are vaccinated to protect the child.

Children with identified mitochondrial diseases are routinely managed carefully by their
physicians with aggressive fever control and hydration. In this context, vaccination of children
with mitochondrial diseases is recommended. In our experience, the vast majority of patients
with mitochondrial diseases receives a full vaccination schedule according to American
Academy of Pediatric guidelines without consequences, particularly when physicians are
sensitive to fever control and hydration. In our patients with mitochondrial disease and autistic
spectrum disorders, the vaccines did not appear related to the neurologic regression.

I will note again that I feel autistic regression as defined is too vague. Were the patients on the
spectrum before the regression? Were they typically developing before the regression?

At least two children were noted to have multiple regressions (a sibling pair). That indicates that
at least in some cases, regressions occurred in people already autistic. There just isnt other
information on this.

Another area I would like to see discussed further is on siblings:

Affected siblings were identified in 35.7% (10 of 28).


Affected how? Mitochondrial disease. But, are they also autistic? It would seem not since they
included one sibling pair.

This is a big question to me. While the spotlight has been shown on the possibility of
mitochondrial disorders being linked to autistic regression, the more general question is more
important: could fevers induced by vaccination result in any regression (autistic or otherwise) in
people with mitochondrial disorders.

Another question in my mind in this study. Are there patients who underwent regression from
non-autistic to autistic) after age 3? According to the Johns Hopkins group, this doesnt happen.
According to them, there is an age window where the regressions could result in autism. This is a
very important question in how these patients might fit in to the broader spectrum of autism.

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CDC | Mitochondrial Disease | Autism Spectrum Disorder (ASD ...
www.cdc.gov/ncbddd/autism/mitochondrial-faq.html
1. Cached
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Feb 26, 2015 - There are many types of mitochondrial disease, and they can affect
different ... may have some of the symptoms/signs of autism, or; may not have any ...
have had regression and some have had a regressive encephalopathy.
What is mitochondria disease? What does it have to do with autism ...
https://www.autismspeaks.org/node/113411
1. Cached
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As a result, mitochondrial disorders can produce a wide variety of symptoms. ... and
underlying mitochondrial dysfunction experienced regression following a ...
Missing: sins

Mitochondrial Disease and Autism | Interactive Autism Network


https://iancommunity.org/cs/asds_related.../mitochondrial_disease
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Nov 22, 2010 - Mitochondrial disease occurs when the mitochondria are not ... itself
that stresses a person with mitochondrial disease, causing regression. ... for
mitochondrial diseases should be done based on a child's signs and symptoms.

NEW STUDY - "Mitochondrial Autism" is Real; Vaccine Triggers ...


www.huffingtonpost.com/.../new-study---mitochondrial_b_147030.html
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Dec 29, 2008 - In fact, the authors wrote that mitochondrial dysfunction may be
present ... Perhaps that is why the very idea of regressive autism has been cause for
derision among many ... Again, biomedical problems - in addition to regression - may
be ... and two of them (8%) showed signs of brain injury from vaccines.

Mitochondrial Disease in Childhood: Nuclear Encoded - NCBI


https://www.ncbi.nlm.nih.gov NCBI Literature PubMed Central (PMC)
by AC Goldstein - 2013 - Cited by 16 - Related articles
Mar 21, 2013 - Primary mitochondrial disease is caused by a defect in the
respiratory .... hypotonia, developmental delay or regression, and hepatic failure that
can be .... (LBSL), with cerebellar ataxia, spasticity, and dorsal column signs [72].

Autism: Metabolism, Mitochondria, and the Microbiome - NCBI


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865378/
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So could an environmental cause be the case in ASD?

Mitochondrial Complex III Deficiency Caused by TTC19 Defects - NCBI


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THC was calculated by regression analysis to be ~ 1.8 g/ml ...

Mitochondrial Dysfunction - Epidemic Answers


https://epidemicanswers.org/epidemic/...causes/mitochondrial-dysfunctio...
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Mitochondrial dysfunction in Autism Spectrum Disorders: cause or effect? ... Fever
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Mitochondrial Medicine - Page 329 - Google Books Result


https://books.google.com/books?isbn=0415390362
Salvatore DiMauro, Michio Hirano, Eric A. Schon - 2006 - Medical
... Sin (11) is changing with time, which makes the problem strongly non-linear. ... is
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section immersion, which is calculated by the linear regression method.

Searches related to sins that-cause-mitochondria-regression-


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A stipulated victim-is visited by a flying wheel-and behind the pictures that if suggestive invisible
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http://extraterrestrialcontact.com/tag/ufos-3/

INTERVIEWS WITH HEROS WHO CONTACT ALIENS & OTHERS, Part 1

Hear Andrew Basiago, Randy Cramer, Ken Johnston, George Green, Sherry Wilde, Miesha
Johnston, Cynthia Crawford, Robert Peralta, Janet Kira Lessin, John Titor II, Reinerio
Hernandez, Hildregard Gmeiser, Karen Christine Patrick, Olaf Jansen and others share
their experiences.

Aloha. Im Dr. Sasha Lessin. Wife Janet and I are hypnotherapists. We specialize in
exploration of nonordinary consciousness, including alien contact.

Collegue Karen Chrisine Patrick joined us in the radio shows below as we interviewed
hero whistleblowers, ET ambassadors and genetic donors.

Click on the sound band, arrows or yellow dot in the upper left-hand corner of the
interviewees photo for each entry below to listen; okay to skip around. Im adding
hotlinks to most of the interviews below. If you click the links, you get extended
information pages to which you can click through for illustrations, experiencer bios an
publications and contact info on each.

Well keep adding to this site.

ALIEN EXPERIENCES ARE USUALLY BENEFICIAL TO CONTACTEE & HUMANITY By Reinerio


Hernandez
Below are several findings from the WORLDS FIRST COMPREHENSIVE ACADEMIC
RESEARCH STUDY ON INDIVIDUALS THAT HAVE HAD UFO RELATED CONTACT EXPERIENCES
WITH NON-HUMAN INTELLIGENCE! http://www.experiencer.org/survey/ Our Executive
Director is Harvard Astrophysicist Dr. Rudy Schild. Our Research Committee Co-Chairs
are 2 retired academic professors Dr. Bob Davis (Neuroscientist) & Dr. Jon Klimo
(Transpersonal Psychology). All of our Phase 1 & Phase 2 research data and our research
methodology is available in our FREE Website: http://www.experiencer.org/survey/

Our initial survey findings, based upon 600 questions and almost 3,300 survey responses,
totally contradict what is being circulated in the Internet and in the field of Ufology.
Over 3,300 participants from over 100 countries

Surveys conducted in 4 languages: English, Spanish, French and German

Memories only from CONSCIOUS EXPLICIT MEMORIES NOT from Hypnotic


Regressions

The following data is only from the ENGLISH LANGUAGE SURVEY

65%, or 1,024 of these individuals have had a witness to the UFO sighting
1,072 have physically seen a Non-Human Intelligent Being
Over 75% of individuals have viewed their physical contact experiences as
Positive
Only 15% have viewed their contact experiences as Negative

The Energy Beings (55%) and Human Looking Being (54%) is the most common
type of being seen by Experiencers and not the Short or Tall Greys

593 individuals have seen an Energy Being

5% view the Energy Being as Mainly Negative

570 individuals have seen a Human Looking Being

5.5% view the Human Looking Being as Mainly Negative

542 individuals have seen Small Grey Being

11.72% view the Small Grey Being as Mainly Negative

498 individuals have seen Ghost/Spirit Being

6.6% view the Ghost/Spirit Being as Mainly Negative


346 individuals have seen Tall Grey Being

10.5% view the Tall Grey Being as Mainly Negative

270 individuals have seen a Reptilian Being

23% view the Reptilian Being as Mainly Negative

238 individuals have seen a Praying Mantis Type Being

9.44% view the Praying Mantis Type Being as Mainly Negative

1,092 individuals stated they saw Other Types of Beings

8.8% view the Other Types of Beings as Mainly Negative

85% have undergone major transformations for the POSITIVE per 75 Life Style
Changes Questions (more spiritual, less egotistical, more concern for the
environment, less concern for monetary values, etc)

50% have reported a medical healing by a non-human intelligent being

80%, or 1,570 have had an Out of Body Experience (OBE)

35% have had a Near Death Experience

32% of those that have had BOTH UFO Contact AND Contact with a Non-Human
Intelligence have had an Abduction

71% state that they are CONTACTEES and NOT ABDUCTEES

84% do NOT want their ET contact to stop

450 individuals have had conscious memories of being aboard a craft

55% have had missing time;

79% state the ETs have a personality

66% have received telepathic messages

the majority of Experiencers have seen non-human intelligent being (NHIB) more
than 10 times;
395 individuals have stated that they believe that they have been involved in
what is commonly called an Alien Breeding Program;

100 individuals have stated they had a MILAB Abduction

83% of Experiencers believe that the non-human intelligent beings (NHIBs) are
somehow related to the Spirit World

95% of Experiencers have had some type of paranormal experience

826 have received information about advanced science or technology

Only 15% have RH Negative blood the national average

Finally, there appears to be a very strong relationship between NDEs and UFO
related Contact (OBEs, Telepathic Communication with Human Looking Beings,
both groups experience numerous physical and psychic changes such as increased
ESP skills, ability to see energy fields, effects on electrical devices, medical
healings, Spirit World connections, and many other similarities)

Below youll find the youtubes and short intos.

ASTRONAUT WHISTLEBLOWER KEN JOHNSTON REVEALS HOW ETS TRAINED HIM TO


DISCLOSE UNTOUCHED NASA PHOTOS OF OPERATING MOONBASES AND ANCIENT RUINS
ON MARS LONG BEFORE ARMSTRONG ARRIVED

Click on the little arrow on the bar below and hear how Johnston got photos showing
mile-high domed spaceports, large cities and ancient ruins on the moon and how his
regression session with Dr. Lessin awakened memories of how extraterrestrials trained
him and other whistleblowers to bring about disclosure of the ET presence on the moon,
Mars and Earth.

Audio Player
http://kcorradio.com/KCOR/Podcasts/Divine-Paradigm/2016/March/Ken-Johnston-
Bret-Sheppard-Anomilies-On-The-Moon-Divine-Paradigm-Dr-Sasha-Lessin-Janet-
Kira-Lessin-KCOR-Digital-Radio-Network.mp3
00:00
02:11
21:38
Use Up/Down Arrow keys to increase or decrease volume.
Click arrow above.

ANDREW BASIAGO REVEALS MARS TRANSPORT, TIME TRAVEL & ROLE OF CIA OPERATIVE
OBAMA ON MARS
Listen to Andrew D. Basiago ~ 03-27-2016 ~ Sacred Matrix on Spreaker.
http://www.spreaker.com/user/aquarianradio/andrew-basiago-alfred-webre-01-03-
2016_2https://www.spreaker.com/user/aquarianradio/andrew-d-basiago-interview-09-21-14