Figure 1 Timeline of largescale genomic analyses. Shown are selected components of work on

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Figure 1 Timeline of large-scale genomic
analyses. Shown are selected components of work
on Several non-vertebrate model organisms (red),
the mouse (blue) and the human (green) from 1990
earlier projects are described in the text.
SNPs, single nucleotide polymorphisms ESTs,
expressed sequence tags.
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Figure 2 Idealized representation of the
hierarchical shotgun sequencing strategy. A
library is Constructed by fragmenting the target
genome and cloning it into a large-fragment
cloning vector here, BAC vectors are shown. The
genomic DNA fragments represented in the library
are then organized into a physical map and
individual BAC clones are selected and sequenced
by the random shotgun strategy. Finally, the
clone sequences are assembled to reconstruct the
sequence of the genome.
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Figure 3 The automated production line for sample
preparation at the Whitehead Institute, Center
for Genome Research. The system consists of
custom-designed factory-style conveyor belt
robots that perform all functions from purifying
DNA from bacterial cultures through setting up
and purifying sequencing reactions.
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Figure 4 Total amount of human sequence in the
High Throughput Genome Sequence (HTGS) division
of GenBank. The total is the sum of finished
sequence (red) and unfinished (draft plus
predraft) sequence (yellow).
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Figure 6 The key steps (ad) in assembling
individual sequenced clones into the draft genome
sequence. A1A5 represent initial sequence
contigs derived from shotgun sequencing of clone
A, and B1B6 arefrom clone B.
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Figure 7 Levels of clone and sequence coverage. A
'fingerprint clone contig' is assembled by using
the computer program FPC84,451 to analyse the
restriction enzyme digestion patterns of many
large-insertclones. Clones are then selected for
sequencing to minimize overlap between adjacent
clones. For a clone to be selected, all of its
restriction enzyme fragments (except the two
vector-insert junction fragments) must be shared
with at least one of its neighbours on each side
in the contig. Once these overlapping clones have
been sequenced, the set is a 'sequenced-clone
contig'. When all selected clones from a
fingerprint clone contig have been sequenced, the
sequenced-clone contig will be the same as the
fingerprint clone contig. Until then, a
fingerprint clone contig may contain several
sequenced-clone contigs. After individual clones
(for example, A and B) have been sequenced to
draft coverage and the clones have been mapped,
the data are analysed by GigAssembler (Fig. 6),
producing merged sequence contigs from initial
sequencecontigs, and linking these to form
sequence-contig scaffolds (see Box 1).
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Figure 37 Functional categories in eukaryotic
proteomes. The classification categories were
derived from functional classification systems,
including the top-level biological function
category of the Gene Ontology project (GO see
http//www.geneontology.org).
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Figure 38 Distribution of the homologues of the
predicted human proteins. For each protein, a
homologueto a phylogenetic lineage was considered
present if a search of the NCBI nonredundant
protein sequence database, using the gapped
BLASTP program, gave a random expectation (E )
value of 0.001. Additional searches for probable
homologues with lower sequence conservation were
performed using the PSI-BLAST program, run for
three iterations using the same cut-off for
inclusion of sequences into the profile328.
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Figure 46 Conserved segments in the human and
mouse genome. Human chromosomes, with segments
containing at least two genes whose order is
conserved in the mouse genome as colour blocks.
Each colour corresponds to a particular mouse
chromosome. Centromeres, subcentromeric
heterochromatin of chromosomes 1, 9 and 16, and
the repetitive short arms of 13, 14, 15, 21 and
22 are in black.
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Figure 2. Flow diagram for sequencing pipeline.
Samples are received, selected, and processed in
compliance with standard operating procedures,
with a focus on quality within and across
departments. Each process has defined inputs and
outputs with the capability to exchange samples
and data with both internal and external entities
according to defined quality guidelines.
Manufacturing pipeline processes, products,
quality control measures, and responsible parties
are indicated and are described further in the
text.
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Figure 3. Anatomy of whole-genome assembly.
Overlapping shredded bactig fragments (red lines)
and internally derived reads from five different
individuals (black lines) are combined to produce
a contig and a consensus sequence (green line).
Contigs are connected into scaffolds (red) by
using mate pair information. Scaffolds are then
mapped to the genome (gray line) with STS (blue
star) physical map information.
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igure 15. Distribution of the molecular functions
of 26,383 human genes. Each slice lists the
numbers and percentages (in parentheses) of
human gene functions assigned to a given category
of molecular function. The outer circle shows the
assignment to molecular function categories in
the Gene Ontology (GO) (179), and the inner
circle shows the assignment to Celera's Panther
molecular function categories (116).
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Figure 16. Functions of putative orthologs across
vertebrate and invertebrate genomes. Each slice
lists the number and percentages (in
parentheses) of "strict orthologs" between the
human, fly, and worm genomes involved in a given
category of molecular function. "Strict
orthologs" are defined here as bi-directional
BLAST best hits (180) such that each orthologous
pair (i) has a BLASTP P-value of 1010 (120), and
(ii) has a more significant BLASTP score than any
paralogs in either organism, i.e., there has
likely been no duplication subsequent to
speciation that might make the orthology
ambiguous. This measure is quite strict and is a
lower bound on the number of orthologs. By these
criteria, there are 2758 strict human-fly
orthologs, and 2031 human-worm orthologs (1523 in
common between these sets).
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