Biology Reference
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understand the rift between them as stemming from commitments to
fundamentally different sorts of practices. In order to explore these dif-
ferences, let me give a more detailed example of each:
: : :
The biologist : Natalie is interested in the problem of alternative
splicing. In particular, she wants to determine how many alter-
native splicing events are conserved between human and mouse,
since the result would suggest the importance of such events
for biological fi tness. First, she downloads the genomes of both
human and mouse from GenBank. Then she downloads large
collections of EST (expressed sequence tag) data from publicly
available databases for both human and mouse. Natalie uses a
freely available piece of software called GENOA to align the
ESTs with the human and mouse genomes. This results in al-
most a million human EST alignments and about half a million
mouse EST alignments. Natalie then writes a program to deter-
mine which of these ESTs, for both mouse and human, contain
alternative splicing events. She uses online databases (EnsMart
and Ensembl) to determine which pairs of human and mouse
genes match one another (are orthologous). This procedure
allows Natalie to identify about two thousand alternatively
spliced EST events that were conserved between human and
mouse. Wishing to validate these results in the wet lab, Natalie
then performs experiments using RT-PCR (real-time polymerase
chain reaction) on RNA from human and mouse tissues, verify-
ing about thirty of the alternative splicing events. 11
The computer scientist : Henry is also interested in alternative
splicing. However, he conceives the problem as one of predicting
de novo which sequences, within a very large sample, map to
exon junctions in the human genome. First, he computes the pa-
rameters of the problem, demonstrating that a brute force search
would require 72 million CPU-years. This fi nding provides the
justifi cation for developing a novel algorithm to speed up the
process. After developing an algorithm he thinks will achieve a
signifi cant speedup, Henry spends several weeks “prototyping”
it in Java. Although the algorithm is successful, it does not run
as fast as Henry requires. He decides to reimplement the algo-
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