Facilitating
in a Human
S. B. Davidson,
Dept.
Genome
and Information
University
of Pennsylvania
Email:
susan@cis.
Department
Science
Dept.
author:
B. Davidson,
Phone
(215)
interesting
lution,
Project
database
complex
challenges:
data
entry
the need to iutegrate
tems which
While
ical
range
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multiple
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and make
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Genome
Center
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of a
acid)
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of
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over
make
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in this
in this
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in
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of the major
schema
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problems
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applications.
at
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perimental
data
forcing
evolution
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and
to
Furthermore
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discussed
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and
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in HGP
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laboratory
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rise
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applications.
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developed
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octhe
experimentation.
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en-
ax a less
az markers
faced
and
techniques
cur
the
involves
markers
Center
se-
Consequently
of Pennsylvania
domain.
*This research was supported
in part by the following grants:
NSF IR19004137, ARO DAAH0493G0,
NIH P50-HG-00425,
NSF
BIR9402292
and ARO DAAL03-89-CO031
PRIME.
on the
directly
of Philadelphia.
One
ify
G’s
chromosomes
The
diflike
400 bases),
time.
Mapping
is the
Genome
University
for
fragments
a
discover-
and
for sequencing
anchoring
Chr22DB,
of four
arranged
means
T’s,
at one
as landmarks.
Philadelphia
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DNA
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DNA
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goal.
the
of
(deoxyribonupairs
G,
practicaf
bases)
is to
is composed
(approximately
mapping
chromosome,
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solu-
set
(HGP)
comprising
techniques
strings
of identifiable
Hospital
im-
are
are not
serve
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of A’s,
there
DNA
has
to
combination,
solutions
to
prob-
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Project
of DNA
Sequencing
intermediate
located
the
broader
bases
(3 biUion
sitions
the
particularly
the
automated
or are inadequate
these
a wide
the
man-
data
their
HGP
dering
as within
where
the
Genome
chromosome
sequence
methods
genome
schema
constraint
data
of complementary
or
short
tire
ambitious
and
up
Although
a confluence
databases,
as well
databases,
Furthermore,
and
multiple
challenges
notebook
Project
complexity
do not
challenges:
to int egrate
laboratory
of biological
intensity
present
which
formats.
Genome
databases
data
need
systems
and
Human
complex
and the
software
models
tion
database
evolution,
agement,
Project
step
of these
chromosomes
molecule
a string.
exact
current
Introduction
made
nucleotides
ing
transformations
Human
Each
ferent
string.
Genome
Genome
a first
core
to express
24 distiuct
double-stranded
cleic
a
of the
the
quencing
Human
to be the
in which
genome.
long,
We
and constraints.
1
Philadelphia
describes
constraints.
goal
human
complexity
of the Philadelphia
database
perceive
a language
and
sequence
to biolog-
imperative.
for these problems,
at the
22, and
sys-
Chromosome
for expressing
89S-0587
Chromosome
what we
tions
and formats.
unique
for
lems:
and
en. upenn. edu
Fax (215)
solving
evo-
in the context
for Human
language
and data
of
management,
necessarily
combination,
a confluence
schema
sources
variety
their
illustrate
present
and constraint
over a wide
challenges
databases,
deductive
databases
PA 19104-6145
eckman~cbil.humg
S98-3490,
Center
Science
of Pennsylvania
Philadelphia,
Entail:
of the
Genome
and Information
University
edu
Susan
of Genetics
of Computer
rspenn. edu,
cis.upenrs.
*
B. Eckman
Abstract
Hmnan
Database
PA 19104-6389
kosky@saul.
Contact
Project
A. S. Kosky
of Computer
Philadelphia,
Transformations
to a number
need
the data
and contains
tables
(incluof com-
to be specified
to be correct.
Another
major
heterogeneous
is
frequently
notebook
as the
protein
ical
bibliographic
genome
laboratory
tems
perform
ject
and
This
different
haps
persist.
ple
queries,
it
is often
models
only
views
increase
in
of the
to
as a whole;
organize
dent
structuring
of
the
The
GenBank
family
is
“standard”
flat-file
variants,
National
veloped
at
ASN.
the
22 [7],
data
cept
from
Each
advantages
that
recent
been
vasive
o A
recent
report
of
[9] listed
that
were
current
data
sources,
among
was
issues
and
that
query
and
(b)
important
data
users,
a query
The
problem
ible
tools
research.
conand
dis-
query
others.
that
they
of
we
are
per-
Energy
In-
of simple
to
with
answer
the
sources
databases,
there
how
we
been
to analyze
a
to
and
to
as follows:
and
a data
trans-
encountered.
language
sample
current
have
and
than
desirable
is organized
transformation
the
used
large
evolution.
techniques
and
shows
We
fail
encountered,
Section
and
problem.
2
A Sample
Data
to
how
conclude
address
discussing
Transformation
The
data
and
notebook
and
difficult
know
little
to
in
for
start
modeled
the
the
the
future
in Chr22DB
archivaJ
HGP
understand,
to nothing
therefore
ing
schemas
databsses
about
what
some
complex
for
those
biology.
a bit
of the
laboratory
highly
molecular
off by explaining
and
and
are
especially
about
terms
who
We will
what
used
is be-
mean.
programs
into
and
information
fact
of
some
technique
for
of their
system
faced:
that
rapidly
HGP’s
View
intermediate
(fragments
and
(a)
the
the
the
attempt
listed
lack
DBMS
of
they
underlying
two
of the Biological
goal
of DNA)
locating
or
we will
consider
probes
and
an
were
them
schema
The
is the
that
an
or data
re-mapping
problem
of
trans-
is
is understandable
applications
evolution
databases.
by
program.
calls
Back-
into
the
We
need
string.
424
interest
is
a linear
ordering
Sequence
cut
the
to be able
of DNA
neighboring
overlap
using
cloned
randomly
into
are then
representing
from
A variety
manipulable
pieces
To discover
pieces
chromo-
positions.
mapping
These
come
ordering
human
(STS’S).
bases).
of two
pieces
Sites
rniUion
it is crucial
sequence
flex-
physicai
experimentally
string.
the
markers
to specific
lothe sake of simplicity,
of
DNA
fragments,
for
Tag
of
pieces
mapping
along
at known
one:
chromosome
(50,000-1
original
only
Sequence
overlapping
bled
this
form
language,
The
markers
some
evoking.
part
A Databaser’s
ground
the
are dis-
is no effective
2.1
of techniques
are used to anchor
cations
on the chromosome.
For
they
the
of schema
for
because
language
constantly
forming
de-
them.
a genome
adequate
using;
onr
is easy
is
of as a
rather
of Chr22DB
hss
this
forms
is highly
paper
that
to capture
arguing
that
a part
problem
it
right
for
is rather
database
of rapid
of this
2 illustrates
problems
a number
et al [10] in an appraisal
create
major
impossible
various
files,
combining
Goodman
to
in a form
reason
be thought
output
– a whole
accep-
are the
computational
whose
in light
remainder
it is used
The
Furthermore,
query
universal
they
can
the
(datalog
transforms
problems
that
and
complex
about
The
by
in which
simple
the
reason
gained
we believe
transformation
relation.
have
yet
and
languages
Chro-
among
the
indicate
single
Los
version,
to a biological
a Department
“summit”
structured
An
and
for
base
advantages
portability,
is one
a declar-
from
of representation,
underscore
to,
queries
for
●
and
it
very
formation
the
1 version
which
are
on
transformations
transformations.
a data
ushas
databases:
formatics
tributed
[8],
view
issues
papers
HGP
group
while
Section
syn-
developed
Center
that,
to data
it
that
is based
query
not
approach
iUustrate
transformations
declarative
have
our
and
approach
languages,
(as in
sources).
for specifying
extensions)
as query
3 describes
is
at the
ASN.
its
While
approach
data
trivial
one knowledge
entry
include
alluding
to
the
hese has its own
expressiveness,
Two
have
oft
there
developed
Phdadelphia
our
the
information.
point:
version
sim-
acceptable
indepen-
numerous
[6],
at least
a sequence
view.
language
with
by the
within
similar
in
a relational
and
developed
or
version
Laboratory
N CBI,
1 version
mosome
also
version
a relational
Alamos
the
same
and
Our
TSL,
fam-
models
is to describe
of data
(as
models
Genbank
data
multiple
model
data
as in the
transformations,
DB.
language,
structurally
per-
beyond
application
to achieve
Thus,
we find numerous
a case
and
data
complexity
necessary
the
increases,
partial,
in Chr22
ative
query,
within
to optimize
a specific
system
performance.
tactic
(Ob-
paper
problem
tance
dat abases
complexity
capture
diilerent
tasks
string
flat-relational
from
of th~
ing
a sample
and
trans-
data
different
multiple
of data
data
a single
between
screens,
to specifying
transformations:
in
or across
purpose
constraints.
databases.
and
As data
may
significantly
and
entry
integration
arisen
which
databases
in schemas
databases
analysis
search
include
personal-computer-bwed
to
of
computa-
complex-relationti
heterogeneity
is likely
Staden,
such
object-oriented
GemStone),
human
data
evolution),
data
The
assoftwaresys-
as pattern-matching,
(Sybase),
(ASN.1),
HGP
involving
biomed-
to
schemas
of dat abases),
the
Genbank,
the
schema
ily
number
and
with
approach
between
(ss with
queries
the
agroting
analysis
the
databases,
and
as well
databases
formations
answer
[1],
[4],
These
Store,
[2];
a principled
packages
of
database,
PIR
[3], FASTA
data
comparison.
databsses
to
Medline,
GDB
multiple,
contents
archival
base,
databases;
as BLAST
problems
and
base,
base,
complex
the
sequence
data
to
software
include
data
notebook
such
tional
acid
data
access
and
augment
These
sequence
map
that
databases
nucleic
the
as
to
by researchers.
such
is
databases
needed
laboratory
posed
problem
remote
their
order
relative
between
in the
ordering
to ascertain
overlaps,
size
reassem-
when
that
sites
in
the
two
pieces
is,
of
the
when
original
of
DNA
can be detected
the
a probe.
The
them,
desired
linear
and
related
and
interest,
and
visible
tion
lines
larger,
quence
contains
of a tiny
1.
become
used
to
size
range
and
time
cloned
be
the
se-
2.2
to
which
at
the
denote
markers
the
(probes).
of
pat-
The
func-
of granularity.
Horizontal
lines
the
sequence
data
-
‘---
to
are:
human
in
J-. I
.. . .
physical
Cloned
of
the
In cloning,
probes
and
In
are
what
and
and
STS’S
carrier
these
STS
It
consists
When
of the
the host
human
Sequence
Tag Sites (STS ‘s).
cells
DNA
DNA
merely
introduced
lations
rather
tributes
for
attribute
defined
cal reaction
pai~
used
as primers
amplification
stages,
each
An amplification
primer
sequences
the
demonstrates
items
a primer
amplification).
several
perature.
less the
within
called
(PCR
reaction
prises
by
intervals
about
test
sequence;
sequence
an
STS
The
proceeding
reaction
are found,
therefore,
its
name,
entire
multiple
2.
sub-
Since
be one
row
relation
rows
in
the
screen
must
be
Chr22DB
schemal
in
of
linkages
a precise
given
primary
rele-
3; this
between
is
re-
semantics
of
the
tables
and
at-
relational
are
the
Figure
below.
Uppercase
keys.
lMIE,
pnblicxmne
)
erwilid,
date-picked,
strand)
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chain
reaction
comtem-
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will not occur
unproperly
spaced,
with
this
database
nested
lational
reaction
Important
including
give
pickmethod,
ions
Aenat
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the
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relevant
denote
Figure
Location).
is shown
schema
ing-temp,
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a chemi-
at a different
a successful
this
used
will
(EER)
to
a form
in
with
data-entry
convey
of the
names
STS (ID,
of sequenced
to start
by the polymerase
containment.
are:
a pair
to
names (SATSRIAIJD,
primer
(ID, pname,
is an interval
the
may
map
relations.
underlying
than
in
melt
STS
at
of
the
must
there
in
and
conceptusJ
Some
produced,
rows
on
of
database
is shown
ions,
pair,
view
the
(STS)
Location
the
are captured
example
STS,
of Chr22DB
schema.
experiments.
An
A
portion
of
are cultured,
are
entered
database.
vant
two
and
to
An
involved,
application
relation
primer
ions
and
data
is
generator
by hand.
data
the
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trans-
applications
of the data
view
a single
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Data
application
schemas.
illu-
of structural
since
and
case
a good
entry
the
notebook
enters
the
provides
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Though
is a special
data
provides
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screen
transformed
we
or interval
vector
two
hand.
entry
to be done
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PCR.condit
in-
the
from
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transformations,
by
complexity
applications,
lab
data
the complexity
that
center.
largely
and
has
spreadnotebook
as directly
at the
data
in structure,
enter
the
done
database.
denoting
2)
maintained
or
entry
between
actual
are
follows,
a fragment
into
cells.
replicas
acid
and
of sources:
preexisting
as well
consuming
handle
to
a variety
involves
been
of the
form
relations
probes
information
in future
of DNA
of the
derived;
laboratory
out
sources
modification
widely
each
mapping
1) Cloned
to be used
nucleic
were
GDB,
centers,
carried
time
underlying
of a Chromosome
in” freezers,
is inserted
or yeast
exact
(PCR
name
site.
from
as
Rewriting
can not
the
differ
..
comes
other
of some
In data
by Chr22DB.
Probes.
bacterial
temperature
Transformation
transformation,
enormously
a database.
some
DNA
melt-
expected
process
the
primers
of the
glamorous,
formations.
-. -.
in
(STS’S).
stored
stored
Cloned
many
used
Sites
probes
the
GDB;
object-oriented
date
a data
a screen
Mapping
Chr22DB
reagents
about
the
and
the
of the
to
such
particularly
L
-. . .
of probes
describe
stage
Database
these
has
and
—
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formation
which
being
from
and
in
briefly
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product;
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from
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m
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from
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each
in Chr22DB
databases
se-
is shown.
. ———
physical
for
databases,
tools
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name,
of
amplified
databases
sheet
whose
Below,
data
archival
1,<+
in
the
a cross-reference
probe
stration
types
the
A Sample
of
Two
of
required
chromosomal
not
represented
it;
of each
this
banding
fragments
sequence.
of DNA
DNA
top
themselves
level
DNA
marker
to
the
which
coarsest
overlapping
substring
Figure
named
temperature
conditions);
the
sequence
thought
At
with
a microscope,
as landmarks
Vertical
a lin-
then
relationship
Figure
is depicted
under
denote
yields
is contained
as regions
its
in
a chromosome
terns
be
ratory
ing
called
disease.
mapping
is illustrated
figure,
pieces
sequence
may
contain
fragment,
probes
such
to inheritable
Physical
quence
The
landmarks
of special
whose
versa.
sequences
shorter
on the
probes
vice
their
much
ordering
on the
map
areas
that
of a third,
ear ordering
in
by showing
sequence
lated
transformation
subrelations
schema
tables.
with
The
a complex
is flattened
value-baxed
atomic
into
re-
linking
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pointers
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of
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The
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ify
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ming
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finally,
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best
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structural
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target
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lan-
it is straightforward
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languages.
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allowing
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code
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The
language
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rently
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distinct
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established
cies,
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straints,
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important
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databases
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or ILOG
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with
in non-recursive
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so that
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limited
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any
data
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gree of rule
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manipulations.
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novel
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structural
contributions
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significant
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incorporate
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to be an extension
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evolution
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features,
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program
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schema-design
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developed.
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on specifying
into
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off
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the
substantial
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and
part
like
of
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graphical
automatically
generate
transformation
Ultimately
we
schema-manipulation
clauses
the
for
relevant
a schema
We
tools
try
constraints
evolution.
have
The
complexity
man
Genome
quency
of
data
Project
schema
incompatible
structures
databases,
evolutions
an archival
genomic
Our
experience
is that
heterogeneous
must
be exchanged,
tools
and
the
databases
necessitates
the
Knowing
is an extremely
Chr22DB
with
the
fre-
tical
number
of
with
which
dress
much
the problem
formations
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all the
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