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Statistics and Data Analysis for Microarrays Using R and
Bioconductor 2nd Edition Sorin Draghici Digital Instant
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Author(s): Sorin Draghici
ISBN(s): 9781439809754, 1439809755
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Year: 2011
Language: english
Computer Science/Bioinformatics
Second
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K10487
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N. F. Britton
Department of Mathematical Sciences
University of Bath
Xihong Lin
Department of Biostatistics
Harvard University
Hershel M. Safer
School of Computer Science
Tel Aviv University
Mona Singh
Department of Computer Science
Princeton University
Anna Tramontano
Department of Biochemical Sciences
University of Rome La Sapienza
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To Jeannette, my better half,
to Tavi, who brightens every day of my life,
and to Althea, whom I miss every day we are not together
This page intentionally left blank
Contents
Preface xxxix
1 Introduction 1
3 Microarrays 39
ix
x Contents
4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
4.2 What is expected from microarrays? . . . . . . . . . . . . . . 70
4.3 Basic considerations of microarray measurements . . . . . . 70
4.4 Sensitivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
4.5 Accuracy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
4.6 Reproducibility . . . . . . . . . . . . . . . . . . . . . . . . . 77
4.7 Cross-platform consistency . . . . . . . . . . . . . . . . . . . 78
4.8 Sources of inaccuracy and inconsistencies in microarray mea-
surements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
4.9 The MicroArray Quality Control (MAQC) project . . . . . . 85
4.10 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
5 Image processing 89
5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
5.2 Basic elements of digital imaging . . . . . . . . . . . . . . . . 90
5.3 Microarray image processing . . . . . . . . . . . . . . . . . . 95
5.4 Image processing of cDNA microarrays . . . . . . . . . . . . 96
5.4.1 Spot finding . . . . . . . . . . . . . . . . . . . . . . . . 99
5.4.2 Image segmentation . . . . . . . . . . . . . . . . . . . 100
5.4.3 Quantification . . . . . . . . . . . . . . . . . . . . . . 106
5.4.4 Spot quality assessment . . . . . . . . . . . . . . . . . 111
5.5 Image processing of Affymetrix arrays . . . . . . . . . . . . . 113
5.6 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
6 Introduction to R 119
In this poem we see that desolation and despair have sealed the
fountain of tears in the widowed wife—that the light of love has
gone from her life and returns only through the influence of
childhood, with all its tender links and memories.
The last song, “Ask Me No More,” is like the sestette in a sonnet
—the application of all the preceding. These influences of the family,
with all its sacred ties and affections, are too much for the strong
and noble soul of the Princess, who throws aside all theories of
intellectual independence for woman, and, yielding to the impulse of
love and affection, proclaims the triumph of the womanly elements
in her nature in the following sweet and tender lines:
And again:
“I felt
Thy helpless warmth about my barren breast
In the dead prime.”
Notice, too, how ubiquitous the babe is. Ida carries it with her
everywhere. It is on her judgment seat, it shares in her song of
triumph when the tournament is ended, and is with her on the
battlefield when she is tending her wounded brothers.
The babe is indeed the heroine of the story, holding the epic
along the channel of its main motive, despite every current and
breeze stirred by foreign elements in its course.
It is not hard to read in this poem Tennyson’s solution of the
woman question, though there are some who maintain that it is
vague and unsatisfactory. Such persons forget that it is the office of
the poet not so much to affirm principles on a subject as to inspire
the sentiments which ought to preside over the solution.
It seems to us that the transfiguration of Ida’s nature under the
influence of the affections is the only solution possible that could be
offered by the poet for the questions raised in “The Princess.” It is
the office of poetry, not to guide the conclusions of the intellect, but
to tone the feelings in accordance with truth and duty. Poetry is not
to teach the truth—it is truth itself.
Those who have the interest of the true advancement of woman
at heart should remember that neither the whole race nor woman
herself can be benefited by any system of education for woman at
variance with Nature and not co-ordinate with the highest needs of
the race. It is idle to discuss the equality or inequality of gifts and
faculties as between man and woman. Every person knows that
woman is not only the equal of man in many respects, but his
superior in not a few; yet this does not justify her in waging a war
with Nature and, with her heart clothed in an iron panoply, riding
forth into the arena of dust and turmoil to perform services for which
the strong hand and knightly heart of man as well as the vocation of
centuries have fitted him alone.
As to her education, that which enables her every faculty to grow
and unfold its beauty and power, with no harm to her distinctive
womanhood—that should be her privilege and right to enjoy,
whether it be obtained in convent or co-education hall. That woman
needs a greater breadth and solidity of intellectual culture goes
without saying, and this for two reasons—to better fit her for the
high moral offices which belong to her domestic mission, and to
keep alive in her a just sympathy with the larger social movements
of which she is the passive, but ought not to be the uninterested
spectator.
If Ida’s theories were carried out, the child element in woman
and the feminine element in man would be crushed out, and it is this
very feminine element in man which gives him moral insight—it
constitutes the poetic side of his nature. Without the feminine
element in his nature Chaucer never could have written “The
Canterbury Tales.”
Ida was right in seeking for a more generous culture, but the
spirit in which she sought it was wrong. Mrs. Browning’s Aurora
Leigh would be an artist first and then a woman. Ida, too, would
crush out the womanly elements in her nature in her eagerness to
satisfy the claims of the intellect. She set the claims of the head
above those of the heart, and, like Aurora Leigh, she failed.
Enthusiasts often point to the glories achieved by women
through the centuries, and make this a pretext for their vagaries and
Utopian dreams. Because Corinna won the lyric prize from Pindar,
and Judith delivered her people from Holofernes, and Joan of Arc
repulsed the English from the walls of Orleans, and Queen Elizabeth
laid the foundation of England’s supremacy upon the sea, is it meet
that the whole social order should be turned upside down and
Nature wounded in its very heart? Such enthusiasts forget that the
mother of Themistocles was greater than the vanquisher of Pindar,
the mother of St. Louis of France greater than the Maid of Orleans,
and the mother of Shakespeare greater than she who held with firm
grasp the sceptre of English sovereignty during the closing years of
the Tudor period.
In spite, therefore, of all theories to the contrary, in spite of
many zealous but misguided women who are looking in the near
future for the reign of woman and the complete subserviency of
man, the true mission of woman is, and always will continue to be,
within the domestic sphere, where she conserves the accumulated
sum of the moral education of the race, and keeps burning through
the darkest night of civilization upon the sacred altar of humanity,
the vestal fires of Truth, Beauty, and Love.
He found in the land of Dante and Michael Angelo fit subjects for his
dramatic monologues. The art world of Italy opened up to Browning
new themes, new thoughts. The intense life of its people, full of the
sweetness and aroma of virtue and the dark tragedy of vice, gave
him scope which he could not find elsewhere. Pity it is that he
presents only the dark side of Italian character. Pity it is that the
paganized and sensual Bishop of the Italian Renaissance depicted by
Browning in “The Bishop Orders His Tomb at St. Praxed’s Church”
did not find setting, in his poems, as a foil to the pure and pious
men and women who prayed before the shrines and in the cloisters
of Italy when the new wine of old classicism poured from Homeric
flasks and casks had intoxicated the head and heart of that garden
of Europe and turned possible saints into satyrs.
De Maistre, the great French publicist, has said that history for
the past three hundred years has been a conspiracy against truth.
Aye, and poetry, too, whose countenance should reflect the beauty
of heavenly truth, often wears the mask of the assassin. To-day
there are so-called advanced and up-to-date scholars in our
universities and clubs who hold that “The Bishop Orders His Tomb at
St. Praxed’s Church” is a true reflection of the religious life of the
Italian Renaissance. They quote Ruskin as saying of that poem:
“I know of no other piece of modern English, prose or poetry, in
which there is so much told as in these lines, of the Renaissance
spirit—its worldliness, inconsistency, pride, hypocrisy, ignorance of
itself, love of art, of luxury, and of good Latin. It is nearly all that I
have said of the Central Renaissance, in thirty pages of the ‘Stones
of Venice,’ put into as many lines, Browning’s being also the
antecedent work.”
We would say just here to students of literature and history: Let
not the shadow of a great literary name overawe you. John Ruskin
did a great deal for art and criticism, but he is far from being an
infallible apostle of truth in either domain; and though he loved the
lowly, brown-hooded friars of St. Francis, this love was not based on
spiritual affinity, but on the poetry and art bound up in their humble
lives.
John Ruskin and Robert Browning, respectively art critic and
poet, have done the religious life of the Italian Renaissance a
grievous wrong—nay, they grossly misrepresent it when they say
that this abnormal picture of a Renaissance Catholic bishop truly
represents and reflects the religious life of Italy at that period. No
doubt but a certain amount of abuses and corruption prevailed in the
Church at that time, largely as a consequence of the worldly spirit
which had gained entrance into it during its exile at Avignon.
However, all was not darkness and sin. The vivifying life of the
Church was not exemplified in the Bishop of St. Praxed’s. As the
great historian of the Popes of the Renaissance, Dr. Ludwig Pastor,
says, “If those days were full of failings and sins of every kind, the
Church was not wanting in glorious manifestations through which
the source of her higher life revealed itself. Striking contrasts—deep
shadows on the one hand and most consoling gleams of sunshine on
the other—are the special characteristics of this period. If the
historian of the Church of the fifteenth century meets with some
unworthy prelates and bishops, he also meets in every part of
Christendom with an immense number of men distinguished for their
virtue, piety and learning, not a few of whom have been, by the
solemn voice of the Church, raised to her altars.”
Limiting ourselves to the most remarkable individuals of the
period of which we are about to treat, we shall mention only the
saints and holy men and women given by Italy to the Church: St.
Bernardine of Siena, of the order of Minorites, whose eloquence won
for him the title of “Trumpet of Heaven and fountain of knowledge”;
around him are grouped his holy brothers in religion, Saints John
Capestran and Jacopo della Marca. St. Antonius, whose unexampled
zeal was displayed in Florence, the very centre of the Renaissance,
had for his disciples blessed Antonio Neyrot of Ripoli and Constanzio
di Fabriano. In the order of St. Augustine are the following who have
been beatified: Andrea, who died at Montereale in 1497; Antonio
Turriani, in 1494. In 1440 St. Frances, the foundress of the Oblates,
was working at Rome. The labors of another founder, St. Francis of
Paula, who died in 1507, belong in part to this period. These names,
to which many more might be added, furnish the most striking proof
of the vitality of religion in Italy at the time of the Renaissance. Such
fruits do not ripen on trees which are “decayed and rotten to the
core.”
Indeed, it is astonishing what nonsense is talked about this
period of the Italian Renaissance, especially as it influenced the
religious life of the people. In one breath our would-be professors
will tell you that the Italian Renaissance movement swept the
Catholic Church into a vortex of paganism—pope, cardinals, bishops,
and all; and in the next they will lead you to believe that the Catholic
Church set its face against the new revival of classical learning,
fearing that the development of the intellect would be prejudicial to
the faith of the people. Either slander will effect its end.
As we write we have before us two historical works of somewhat
recent publication: “Books and Their Makers During-the Middle
Ages,” by George Haven Putnam, A.M., and “A General History of
Europe,” by Professors Thatcher and Schwill, of Chicago University.
As the latter is now used as a text-book in many American High
Schools, we will deal with its worth and wisdom first.
There is but one Chicago University in the world, and we might
expect its distinguished professors of medieval and modern
European history to understand at least the elementary truths of the
Catholic Church and something of its spirit and policy.
Let us examine for a moment some of the statements contained
in this “General History of Europe,” by Professors Thatcher and
Schwill. Here is a choice morsel which will amuse the student of
Church history. The topic is “The Church and Feudalism.” The author
says: “As late as the eleventh century it was not at all uncommon for
the clergy to marry. Since fiefs were hereditary, it seemed perfectly
proper that their children should be provided for out of the Church
lands which they held. But unless all their children became
clergymen these lands would pass into the hands of laymen and
therefore be lost to the Church. One of the purposes of the
prohibition of the marriage of the clergy was to prevent this
alienation and diminution of the Church lands.”
And this little paragraph dealing with the Italian Renaissance,
found on page 264 of the same work: “Medieval life knew nothing of
the freedom, beauty and joy of the Greek world. . . . The medieval
man had no eye for the beauty of nature. To him nature was evil.
God had indeed created the world and pronounced it very good, but
through the fall of man all nature had been corrupted. Satan was
now the prince of the world. As a result no one could either study or
admire nature.” Pray note the force of the auxiliary “could.”
Just think of it! A Catholic—a medieval Catholic—was forbidden
to look at or admire a flower, a forest, or a mountain peak. How so
much of nature got mixed up in the singing of “Old Dan Chaucer,” a
Catholic poet of the fourteenth century, we know not. ’Tis a mystery.
Chaucer is essentially the poet of the daisy, and robed it in verse
long before Burns turned it over with his plough.
Then we have the brown-hooded and gentle Friar, St. Francis of
Assisi, who was wont to call the birds of the air and the beasts of
the field his brothers, and who composed canticles to the winds, the
flowers and the sun. Did the erudite professors of Chicago University
ever make a study of Gothic architecture, the distinct inspiration and
creation of medieval times? If so, they will remember that plants and
flowers play, in symbolism, an important part in ornamentation. The
hatred of nature as well as the hatred of art imputed to the early
Christians is simply a “fable convenue,” manufactured by the
partisan and superficial historian who is either too dishonest or
indolent to state or reach the real facts.
It is enough to say that Professors Thatcher and Schwill’s work is
actually teeming with historical inaccuracies and gross
misrepresentations of the Catholic Church. Whether by inference or
blunt statement, these two professors have written themselves down
in the pages of their history either as ignorant or dishonest
historians, and it is unworthy of a presumably great university, such
as Chicago, to give its imprimatur to such unreliable and unscholarly
works.
But lest we may not have convicted as yet Professors Thatcher
and Schwill of having misrepresented the truth, life and policy of the
Catholic Church in the pages of their history, we shall cite one more
paragraph found on page 172. It deals with monasticism. The author
says: “The philosophic basis of asceticism is the belief that matter is
the seat of evil, and therefore that all contact with it is
contaminating. This conception of evil is neither Christian nor
Jewish, but purely heathen. Jesus freely used the good things of this
world and taught that sin is in nothing external to man, but has its
seat only in the heart. But His teaching was not understood by His
followers. The peculiar form which this asceticism in the Church took
is called monasticism. . . . After about 175 A.D. the Church rapidly
grew worldly. As Christianity became popular large numbers entered
the Church and became Christians in name; but at heart and in life
they remained heathen. The bishops were often proud and haughty
and lived in grand style. Those who were really in earnest about
their salvation, unsatisfied with such worldliness, fled from the
contamination in the Church and went to live in the desert and find
the way to God without the aid of the Church: her means of grace
were for common Christians. Those who would could obtain, by
means of asceticism and prayer, all that others received by means of
the sacraments of the Church. There were to be two ways of
salvation: one through the Church and her means of grace; the
other through asceticism and contemplation.”
There is assuredly something of the historical naïveté of the
schoolboy in the above. Mark when the Christian Church became
corrupt—nearly one hundred and fifty years before it was upheld by
the arm of Constantine and when it had been hiding for more than
one hundred years in the Catacombs carving and painting in symbol
the truths and mysteries of God. This was the corruption, that as
Christ had birth in the lowly manger of Bethlehem so the Church, His
Spouse, was cradled in humility, hidden away from the purple rage
of the Cæsars, and, like a little child whose dreams are of the past
and the future, was rudely fashioning her life and soul in terms of
eternity, in symbols of the palm, the dove and the lamb.
Now let us cite from Putnam’s “Books and Their Makers in the
Middle Ages” an instance of historical contradiction within the
compass of three pages. It is said that he who misrepresents the
truth must have a good memory, but the author of “Books and Their
Makers in the Middle Ages” is evidently devoid of that faculty,
otherwise he would not have contradicted himself in almost
succeeding pages of his work. Here is the contradiction. He is
speaking of book-making at the time of the Italian Renaissance. On
page 331, Vol. I., the author says: “A production of Beccadelli’s,
perhaps the most brilliant of Alfonso’s literary protégés, is to be
noted as having been proscribed by the Pope, being one of the
earliest Italian publications to be so distinguished. Eugenius IV.
forbade, under penalty of excommunication, the reading of
Beccadelli’s “Hermaphroditus,” which was declared to be contra
bonos mores. The book was denounced from many pulpits, and
copies were burned, together with portraits of the poet, on the
public squares of Bologna, Milan and Ferrara.”
On page 333 of the same volume Putnam writes—and we beg
the reader will compare carefully the two statements: “Poggio is to
be noted as a free thinker who managed to keep in good relations
with the Church. So long as free thinkers confined their audacity to
such matters as form the topic of Poggio’s ‘Facetiae,’ Beccadelli’s
‘Hermaphroditus’ or La Casa’s ‘Capitolo del Farno’ the Roman Curia
looked on and smiled approvingly. The most obscene books to be
found in any literature escaped the Papal censure, and a man like
Aretino, notorious for his ribaldry, could aspire with fair prospects of
success to the scarlet of a Cardinal.”
These are the kind of books that stuff the shelves of the libraries
in our great secular universities.
There is perhaps no other period in the history of the world that
requires more careful investigation than that of the Renaissance in
Italy, and this because of its complex character. Speaking of this
complexity Dr. Pastor says: “In the nature of things it must be
extremely difficult to present a truthful picture of an age which
witnessed so many revolutions affecting almost all departments of
human life and thought, and abounded in contradictions and
startling contrasts. But the difficulty becomes enormously increased
if we are endeavoring to formulate a comprehensive appreciation of
the moral and religious character of such an epoch. In fact in one
sense the task is an impossible one. No mortal eye can penetrate the
conscience of a single man; how much less can any human intellect
strike the balance between the incriminating and the extenuating
circumstances on which our judgment of the moral condition of such
a period depends, amid the whirl of conflicting events. In a rough
way, no doubt, we can form an estimate, but it can never pretend to
absolute accuracy. As Burckhardt, author of ‘The Civilization of the
Period of the Renaissance in Italy,’ says: ‘In this region the more
clearly the facts seem to point to any conclusion the more must we
be upon our guard against unconditional or universal assertions.’”
It were well assuredly if some of our professors of history in the
great secular universities—professors who assume to understand the
Catholic Church and her policy better than her own clergy and laity—
it were well, we say, if these would lay to their historical souls
Pastor’s judicial words ere they indict the “Renaissance Period” and
blacken the character of its popes, its prelates and its people.
The truth is that few if any non-Catholic students read Catholic
historical works to-day. Jansen’s great work, dealing with the social
and religious life of Germany in the period that preceded the advent
of Luther, is considered to be the last word on this debatable
ground, and yet how many non-Catholic students have ever opened
its pages? The same may be said of Pastor’s monumental work.
“Lives of the Popes Since the Close of the Middle Ages.” When this
ignorance of Catholic fact is supplemented by the reading of such
misrepresentation as is found in Browning’s poem, “The Bishop
Orders His Tomb,” what hope can there be of justice to Catholic truth
and the Catholic faith in our great secular universities?
We see, then, that not alone are the facts of history falsified, but
the genius of the poet is enlisted to give glamor and glow to the
historical slander.
Take again Tennyson’s poem, “St. Simeon Stylites.” This is a
satire on ascetic life. Tennyson was a Broad Churchman, and it is
said that he was particularly careful not to write anything that would
offend the religious feelings of any of his friends. He saw, however,
at the time of the “Oxford Movement,” the English mind in certain
quarters look with favor on monasticism, and he wrote “St. Simeon
Stylites” as a rebuke to the movement. But is it a true picture of the
spirit and life of those early hermits of the desert? Not at all.
Tennyson as a satirist did not aim at truth, but rather at
exaggeration. So he puts into the mouth of this pillar-fixed saint
these words of pride:
THE DEGRADATION OF
SCHOLARSHIP
THE DEGRADATION OF SCHOLARSHIP.
“Or a sonnet with flowery marge to the Reverend Don So and So,
Who is Dante, Boccaccio, Petrarca, St. Jerome and Cicero.
‘And moreover’ (the sonnet goes rhyming), ‘the skirts of St. Paul has
reached,
Having preached us those six Lent-lectures more unctuous than ever
he preached.’
Noon strikes,—here sweeps the procession! our Lady borne smiling
and smart
With a pink gauze gown all spangles and seven swords stuck in her
heart!
Bang-whang-whang goes the drum, tootle-te-tootle the fife;
No keeping one’s haunches still: it’s the greatest pleasure in life.”
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