Reading Practice

Life code: unlocked!

{A} On an airport shuttle bus to the Kavli Institute for Theoretical Physics in Santa Barbara,
Calif., Chris Wiggins took a colleague’s advice and opened a Microsoft Excel spreadsheet.
It had nothing to do with the talk on biopolymer physics he was invited to give. Rather the
columns and rows of numbers that stared back at him referred to the genetic activity of
budding yeast. Specifically, the numbers represented the amount of messenger RNA
(MRNA) expressed by all 6,200 genes of the yeast over the course of its reproductive
cycle. “It was the first time I ever saw anything like this,” Wiggins recalls of that spring day
in 2002. “How to make sense of all this data?”

{B} Instead of shirking from this question, the 36-year-old applied mathematician and
physicist at Columbia University embraced it-and now six years later he thinks he has an
answer. By foraying into fields outside his own, Wiggins has drudged up tools from a
branch of artificial intelligence called machine learning to model the collective protein-
making activity of genes from real-world biological data. Engineers originally designed
these tools in the late 1950s to predict output from input. Wiggins and his colleagues have
now brought machine learning to the natural sciences and tweaked it so that it can also tell
a story-one not only about input and output but also about what happens inside a model of
gene regulation, the black box in between.

{C} The impetus for this work began in the late 1990s, when high-throughput techniques
generated more mRNA expression profiles and DNA sequences than ever before, “opening
up a completely different way of thinking about biological phenomena,” Wiggins says. Key
among these techniques were DNA microarrays, chips that provide a panoramic view of
the activity of genes and their expression levels in any cell type, simultaneously and under
myriad conditions. As noisy and incomplete as the data were, biologists could now query
which genes turn on or off in different cells and determine the collection of proteins that
give rise to a cell’s characteristic features, healthy or diseased.

{D} Yet predicting such gene activity requires uncovering the fundamental rules that govern
it. “Over time, these rules have been locked in by cells,” says theoretical physicist Harmen
Bussemaker, now an associate professor of biology at Columbia. “Evolution has kept the
good stuff.” To find these rules, scientists needed statistics to infer the interaction between
genes and the proteins that regulate them and to then mathematically describe this
network’s underlying structure-the dynamic pattern of gene and protein activity over time.
But physicists who did not work with particles (or planets, for that matter) viewed statistics
as nothing short of an anathema. “If your experiment requires statistics,” British physicist
Ernest Rutherford once said, “you ought to have done a better experiment.”

{E} But in working with microarrays, “the experiment has been done without you,” Wiggins
explains. “And biology doesn’t hand you a model to make sense of the data.” Even more
challenging, the building blocks that makeup DNA, RNA, and proteins are assembled in
myriad ways; moreover, subtly different rules of interaction govern their activity, making it
difficult, if not impossible, to reduce their patterns of interaction to fundamental laws. Some
genes and proteins are not even known. “You are trying to find something compelling about
the natural world in a context where you don’t know very much,” says William Bialek, a

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biophysicist at Princeton University. “You’re forced to be agnostic.” Wiggins believes that
many machine-learning algorithms perform well under precisely these conditions. When
working with so many unknown variables, “machine learning lets the data decide what’s
worth looking at,” he says.

{F} At the Kavli Institute, Wiggins began building a model of a gene regulatory network in a
yeast-the set of rules by which genes selectively orchestrate how vigorously DNA is
transcribed into mRNA. As he worked with different algorithms, he started to attend
discussions on gene regulation led by Christina Leslie, who ran the computational biology
group at Columbia at the time. Leslie suggested using a specific machine-learning tool
called a classifier. Say the algorithm must discriminate between pictures that have bicycles
in them and pictures that do not. A classifier sifts through labeled examples and measures
everything it can about them, gradually learning the decision rules that govern the
grouping. From these rules, the algorithm generates a model that can determine whether or
not new pictures have bikes in them. In gene regulatory networks, the learning task
becomes the problem of predicting whether genes increase or decrease their protein-
making activity.

{G} The algorithm that Wiggins and Leslie began building in the fall of 2002 was trained on
the DNA sequences and mRNA levels of regulators expressed during a range of conditions
in yeast-when the yeast was cold, hot, starved, and so on. Specifically, this algorithm-
MEDUSA (for motif element discrimination using sequence agglomeration) -scans every
possible pairing between a set of DNA promoter sequences, called motifs, and regulators.
Then, much like a child might match a list of words with their definitions by drawing a line
between the two, MEDUSA finds the pairing that best improves the fit between the model
and the data it tries to emulate. (Wiggins refers to these pairings as edges.) Each time
MEDUSA finds a pairing, it updates the model by adding a new rule to guide its search for
the next pairing. It then determines the strength of each pairing by how well the rule
improves the existing model. The hierarchy of numbers enables Wiggins and his
colleagues to determine which pairings are more important than others and how they can
collectively influence the activity of each of the yeast’s 6,200 genes. By adding one pairing
at a time, MEDUSA can predict which genes ratchet up their RNA production or clamp that
production down, as well as reveal the collective mechanisms that orchestrate an
organism’s transcriptional logic.

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Questions 1-6
The reading passage has seven paragraphs, A-G

Choose the correct heading for paragraphs A-G from the list below.

Write the correct number, i-x, in boxes 1-6 on your answer sheet.
List of Headings

(I) The search for the better-fit matching between the model and the gained figures to foresee the
the genes

(II) The definition of MEDUSA

(III) A flashback of commencement for a far-reaching breakthrough

(IV) A drawing of the gene map

(V) An algorithm used to construct a specific model to discern the appearance of something new
effort of Wiggins and another scientist
(VI) An introduction of a background tracing back to the availability of mature techniques for detai
on genes
(VII) A way out to face the challenge confronting the scientist on the deciding of researchable data

(VIII) A failure to find out some specific genes controlling the production of certain proteins
(IX) The use of a means from another domain for reference
(X) A tough hurdle on the way to find the law governing the activities of the genes

Example: Paragraph A III

1..................... Paragraph B

2..................... Paragraph C

3..................... Paragraph D

4..................... Paragraph E

5..................... Paragraph F

6..................... Paragraph G

Questions 7-9
Do the following statements agree with the information given in Reading Passage 1? In
boxes 7-9 on your answer sheet, write
TRUE if the statement is True
FALSE if the statement is false

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NOT GIVEN If the information is not given in the passage
7..................... Wiggins is the first man to use DNA microarrays for the research on genes.

8..................... There is almost no possibility for the effort to decrease the patterns of
interaction between DNA, RNA, and proteins.

9..................... Wiggins holds a very positive attitude on the future of genetic research.

Questions 10-13
Complete the following summary of the paragraphs of Reading Passage, using No More
than three words from the Reading Passage for each answer. Write your answers in boxes
10-13 on your answer sheet.
Wiggins states that the astoundingly rapid development of techniques concerning the component
aroused the researchers to look at 10..................... from a totally new way. 11..................... is the
soul of these techniques and no matter what the 12..................... were, at the same time they can
whole picture of the genes’ activities as well as 13..................... in all types of cells. With these tec
scientists could locate the exact gene which was on or off to manipulate the production of the pro

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Solution:
1. ix 8. TRUE
2. vi 9. NOT GIVEN
10. BIOLOGICAL
3. x
PHENOMENA
4. vii 11. DNA MICROARRAYS
5. v 12. (MYRIAD) CONDITIONS
13. THEIR EXPRESSION
6. i
LEVELS
7. NOT
GIVEN

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