Qurate Help
Qurate allows you to view quantitative events from isotopically
labeled peptide experiments in several
different ways, and to judge them as 'good' or 'bad' events (or leave
them marked as 'unknown'). 'Bad'
events can be filtered out of the pepXML file in which they were
observed.
Qurate contains
a robust workflow for selecting which events you wish to curate.
Curation Interface
Properties
The Properties table shows you information about the quantitative
event -- quantitative ratio, light and heavy areas, etc. Multiple
overlapping events (same peptide, same charge, similar retention time)
may be
rolled into a single event if they have similar ratios. Any overlapping
events
other than the one described in these properties will appear in
'OtherEventScans' and 'OtherEventMZs'.
Algorithmic Assessment
When Qurate builds charts for an event, it also runs a subprogram that
uses several heuristics to identify events that "look" bad. These
events may have coeluting peaks one Dalton below the monoisotope; or
they may have very different peak distributions between heavy and
light; or, when calculating its own ratio for the event using only one
peak, that ratio may be very different than what the quantitation
algorithm produced. If any of these conditions holds true, the
event will be marked in red in this area, and details will be given.
Curation
Provide your assessment of the current quantitative event here. You can
describe the quantitative event as "Bad" or "Good", or leave it as
unknown. You can do the same with the identification itself --
sometimes it will be clear from the charts that the identification is
probably wrong (e.g., the predicted monoisotopic mass is not the actual
monoisotopic mass). You can also type comments on the current
quantitative event into the text box. Your assessments and
comments will not be saved unless you explicitly save your changes (see
'Actions', below).
Theoretical Peaks
This small graph shows the theoretical distribution of light and heavy
peaks for a peptide of
this mass, assuming that the ratio identified for this quantitative
event is correct.
Event Control Buttons
The left and right arrows navigate the loaded quantitative events one
by one. The "Show All" button brings up a window with a table
containing all events; you can use this table to navigate to any event,
and to sort events in several ways.
Charts
The charts help you assess the quality of quantitative events.
- Intensity Sum: A plot of
the intensities summed over all of the scans within the range of the
quantitation event. Blue
indicates intensities that are within a
narrow PPM window around each isotopic peak. Green lines indicate
monoisotopic light and heavy peaks, and yellow lines indicate
non-monoisotopic peaks.
- Spectrum: A heatmap showing the intensity of the region of
spectra around the quantitative event. Higher intensities are darker
blue. Grey areas on the left and
right indicate areas not used by the
quantitative algorithm. Horizontal axis shows increasing
scan number, Vertical axis shows increasing m/z. Red tick marks on the
left and right indicate the light and heavy monoisotopic m/z values.
Red 'X' marks indicate
identification events.
- Scans: A separate chart for each scan, showing peak
intensities. All intensities are normalized to the highest-intensity
value in any scan (which may or may not be included in the peptide
quantitation). Vertical green
and yellow lines
indicate monoisotopic
and non-monoisotopic peak m/z values, respectively. Scan numbers
are given at the left -- numbers in green
were used in quantitation, numbers in red were not.
- 3D: A 3D representation of the same data in the Spectrum
chart. Perspective is that of someone standing at a scan higher than
the last scan shown on the chart, near the m/z of the light
monoisotopic peak. Z axis is intensity. Solid red lines indicate the
light and heavy monoisotopic peaks. Dashed red lines indicate the
beginning and end of algorithm quantitation. Blue 'X' marks
indicate the event used in this
quantitative event. Yellow
'X' marks indicate other identification
events folded into this representation.
Selecting Events for Chart Creation
There are two ways to select quantitative events for chart creation:
from a PepXML file (peptide level), or from a ProtXML file (protein
level).
Peptide Level
To select and build charts for events by peptide identification, you
will need to provide a PepXML file, and mzXML file or directory of
mzXML files, and an output directory. You can do this from the
Tools menu, action "Create Charts...". You may also supply
minimum PeptideProphet probabilities ("minpprophet"),
particular
fraction names within the PepXML file ("fractions"),
output HTML and
tab-separated-value files ("outhtml"
and "outtsv"), particular
peptides
to investigate, particular associated proteins to investigate, and
individual scan numbers, as well as a number of advanced arguments,
described within the program, that control the details of how the
charts are made. When all of these parameters are selected, press
"Execute" to immediately build
the charts and load them into the
graphical interface.
Protein Level
For selecting events by protein identification, Qurate provides a
detailed interface that allows you to choose only those quantitative
events that you are interested in. Since generating the charts
takes some amount of time, and reviewing them manually takes more time,
you may wish to restrict your chart creation to, e.g., only events with
extreme ratios, or events for proteins with extreme ratios.
This workflow is accessed via the "Open
ProtXML File" option under the "File"
menu (or by pressing Ctrl-P).
You will need to provide a ProtXML file, a directory containing all
relevant
mzXML files, and an output directory for the charts. You may also
specify the pepXML file explicitly (overriding the value in the ProtXML
file) and provide a file that maps protein accession numbers to gene
symbols
("protgenefile"), an output
file for all the quantitative events
("out"), a restrictive list of
proteins to consider ("proteins"),
a minimum ProteinProphet probability for proteins to consider
("minproteinprophet"), and a
maximum low protein ratio and minimum high ratio to consider ("maxlowratio" and "minhighratio" -- proteins will only
be included if they fit at least one of those ratio bounds). The
optional "appendoutput"
argument controls
whether, if an output file is provided that already exists, the new
events will be appended to the existing events in the file or will
overwrite the current file.
When you have provided these arguments, press "Execute".
This will bring up a new window with a table containing one row per
protein. You can save this table to a file for future reference
("Save Table"). This
table can be sorted on any column. You can select rows (proteins)
manually, or you can click and drag on the histogram of log protein
ratios at the bottom of the window to specify low and high
ratios. As you change these values, green areas will appear to
the left (lower ratio) and right (higher ratio) of the region you
select. Solid vertical line indicates 1:1 ratio. Proteins
with ratios more "extreme" than this region will
be retained in the table; all others will be removed. The "Select All Visible" button will
select all proteins currently
visible in the table. Once you have selected the proteins you
want, press "Show Events".
The next window shows a table with one row per quantitative event, from
all the proteins you selected, sortable on all columns. You may
see
multiple quantitative events for the same peptide. Any
events that are already loaded by Qurate will be greyed out. The
quantitative ratio for the event is displayed numerically, and also (in
log scale) as a graphical slider. This window also has a
log-ratio histogram that you can use to restrict the table to only
extreme-ratio events, but in this window, checkboxes at the left are used for
the actual selection. The checkbox on the first row selects or
deselects all events.
You can view more information
about each event by pressing "Show
Event Properties". The "Show
Protein Table" button opens a table with one row per protein and
another log-ratio histogram. You can select a row in this table
to populate the histogram with the events from that protein, and then
restrict the event ratios to extreme ratios in the usual manner; as you
drag the selection area, events in the event table will be checked or
unchecked appropriately. On this histogram, solid vertical line
indicates 1:1 ratio and dashed vertical line indicates the protein
ratio. The Protein Table also includes a scatterplot showing each
quantitative event in log-ratio space, color-coded by peptide; the Y
axis on this chart simply separates the peptides vertically.
When you
select a set of events and press "Build
Selected Charts", the charts
will be built and loaded into the main Qurate interface; this can take
quite some time (many seconds per event), and a status bar will
indicate
progress. Any events for the same peptide, within the same charge
state, with the same modifications, with similar ratios, will be
bundled into a single set of charts; curation performed on one of them
will apply to all.
Menu Actions
- File Menu
- Open Event File: Pulls
up the contents of a previously-saved quantitative event .tsv file in
the main interface
- Open ProtXML File:
Begins the "Protein Level" workflow described above
- Save: Save your assessments to a .tsv file that may be
loaded by Qurate at a later time.
- Exit: Quits Qurate without saving changes.
- Tools Menu
- Create Charts: Opens a
very simple interface for creating charts for all events from a pepXML
file that match a set of criteria (can specify peptides, proteins,
PeptideProphet probability cutoff)
- Filter PepXML...:
Filter all of your 'Bad' assessments out
of the pepXML file that they
came from. You must specify both the source pepXML file and the output
pepXML file (which may be the same)
- Summary Charts:
Displays summary charts describing the currently-displayed
events.
- Log Ratio Chart: a scatterplot showing, on the X axis, log
ratio as reported by the quantitation algorithm, and, on the Y axis,
log ratio as determined by single-peak quantitation. Red points
are algorithmically assed as "bad". Clicking on any point
displays
that event in the main interface.
- Help Menu
- Help: Displays this
manual
- About: Displays basic
information about Qurate