diff --git a/CHANGES.md b/CHANGES.md
index b710544..374e0dd 100644
--- a/CHANGES.md
+++ b/CHANGES.md
@@ -1,5 +1,11 @@
 # CHANGES
 
+## 3.5.0
+
+* Loads vagrent cache into IntervalTree to speed up processing by:
+  * reducing redundant/random disk access
+  * reducing repeated decompression of same data when events are local to each other
+
 ## 3.4.0
 
 * Add Dockerfile and supporting scripts
diff --git a/Dockerfile b/Dockerfile
index 49d3142..9661a31 100644
--- a/Dockerfile
+++ b/Dockerfile
@@ -52,7 +52,7 @@ FROM ubuntu:16.04
 
 LABEL maintainer="cgphelp@sanger.ac.uk" \
       uk.ac.sanger.cgp="Cancer, Ageing and Somatic Mutation, Wellcome Trust Sanger Institute" \
-      version="3.4.0" \
+      version="3.5.0" \
       description="VAGrENT genome annotation docker"
 
 RUN apt-get -yq update
diff --git a/Makefile.PL b/Makefile.PL
index bf98a2f..c2318d4 100755
--- a/Makefile.PL
+++ b/Makefile.PL
@@ -55,6 +55,7 @@ WriteMakefile(
                     'Sort::Key' => '1.33',
                     'TAP::Harness' => '3.33',
                     'Try::Tiny' => '0.22',
+                    'Set::IntervalTree' => '0.12',
                    }
 );
 
diff --git a/bin/AnnotateVcf.pl b/bin/AnnotateVcf.pl
index e86aa63..ebe5dd8 100755
--- a/bin/AnnotateVcf.pl
+++ b/bin/AnnotateVcf.pl
@@ -404,9 +404,11 @@ sub make_process_log {
 
 sub get_annotator {
 	my $options = shift;
+  my $sorted = $options->{'sorted'};
+  $sorted = 1 if(-e $options->{'input'}.'.tbi');
 
   # creating an EnsemblTranscriptSource using the Ensembl registry
-	my $ts = Sanger::CGP::Vagrent::TranscriptSource::FileBasedTranscriptSource->new('cache' => $options->{'cache'});
+	my $ts = Sanger::CGP::Vagrent::TranscriptSource::FileBasedTranscriptSource->new('cache' => $options->{'cache'}, 'sorted' => $sorted);
 
 	# creating an AnnotatorCollection
 	my $annotator = Sanger::CGP::Vagrent::Annotators::AnnotatorCollection->new(
@@ -473,7 +475,7 @@ sub option_builder {
     'p|process=n' => \$opts{'process'},
     'sp|species=s' => \$opts{'species'},
     'as|assembly=s' => \$opts{'assembly'},
-
+    'u|sorted' => \$opts{'sorted'},
   );
 
   pod2usage() if($opts{'help'});
@@ -537,4 +539,6 @@ =head1 SYNOPSIS
 
     --tabix     (-t)      bgzip and tabix index the output file (will generate the .gz version of the -o option)
 
+    --sorted    (-s)      Input is sorted - lower memory requirement, automatic if *.tbi found
+
 =cut
diff --git a/lib/Sanger/CGP/Vagrent.pm b/lib/Sanger/CGP/Vagrent.pm
index 1691f7d..b52c619 100644
--- a/lib/Sanger/CGP/Vagrent.pm
+++ b/lib/Sanger/CGP/Vagrent.pm
@@ -26,7 +26,7 @@ use strict;
 use Const::Fast qw(const);
 
 use base 'Exporter';
-our $VERSION = '3.4.0';
+our $VERSION = '3.5.0';
 our @EXPORT = qw($VERSION);
 
 1;
diff --git a/lib/Sanger/CGP/Vagrent/TranscriptSource/FileBasedTranscriptSource.pm b/lib/Sanger/CGP/Vagrent/TranscriptSource/FileBasedTranscriptSource.pm
index d198336..d8a4e4a 100644
--- a/lib/Sanger/CGP/Vagrent/TranscriptSource/FileBasedTranscriptSource.pm
+++ b/lib/Sanger/CGP/Vagrent/TranscriptSource/FileBasedTranscriptSource.pm
@@ -31,6 +31,7 @@ use Const::Fast qw(const);
 
 use Bio::DB::HTS;
 use Bio::DB::HTS::Tabix;
+use Set::IntervalTree;
 
 use Sanger::CGP::Vagrent::Data::Transcript;
 use Sanger::CGP::Vagrent::Data::Exon;
@@ -118,9 +119,43 @@ sub _generateLocationString {
   return $gr->getChr.':'.$gr->getMinPos.'-'.$gr->getMaxPos;
 }
 
+sub _tabix_to_interval_tree {
+  my ($self, $chr) = @_;
+  return 1 if defined $self->{_cache_iTree}->{$chr};
+
+  my $full_tree = {};
+  if ($self->{_sorted}) {
+    $self->{_cache_iTree} = $full_tree;
+  }
+  else {
+    $full_tree = $self->{_cache_iTree};
+  }
+
+  my %collated;
+  $self->{_cache_tbx} = Bio::DB::HTS::Tabix->new(filename => $self->{_cache}) unless defined $self->{_cache_tbx};
+  my $iter = $self->{_cache_tbx}->query_full($chr);
+  return 1 unless defined $iter;
+    while(my $line = $iter->next) {
+    my ($chr, $s, $e, $object) = (split /\t/, $line)[0,1,2,6];
+    # +1 on end to convert to 1 bases, tabix module would handle this
+    my $this_loci = sprintf '%s:%d:%d', $chr, $s, $e+1;
+    push @{$collated{sprintf '%s:%d:%d', $chr, $s, $e+1}}, $object;
+  }
+
+  my $chr_tree = Set::IntervalTree->new();
+  for my $loci(keys %collated) {
+    my ($chr, $s, $e) = split ':', $loci;
+    $chr_tree->insert($collated{$loci}, $s, $e);
+    delete $collated{$loci};
+  }
+  $full_tree->{$chr} = $chr_tree;
+  return 1;
+}
+
 sub _getTranscriptsFromCache {
   my ($self,$gp) = @_;
-  $self->{_cache_tbx} = Bio::DB::HTS::Tabix->new(filename => $self->{_cache}) unless defined $self->{_cache_tbx};
+  my $chr = $gp->getChr();
+  $self->_tabix_to_interval_tree($chr);
   my $min;
   my $max = $gp->getMaxPos + $SEARCH_BUFFER;
   if($gp->getMinPos() < $SEARCH_BUFFER){
@@ -128,27 +163,39 @@ sub _getTranscriptsFromCache {
   } else {
     $min = ($gp->getMinPos - $SEARCH_BUFFER);
   }
-  my $iter = $self->{_cache_tbx}->query_full($gp->getChr(),$min,$max);
-  return undef unless defined $iter;
-  my $out = undef;
-  while(my $ret = $iter->next){
-    my $raw = (split("\t",$ret))[6];
-    my $VAR1;
-    eval $raw;
-    $VAR1->{_cdnaseq} = $self->_getTranscriptSeq($VAR1);
-    push @$out, $VAR1;
+  my @data = ();
+  @data = @{$self->{_cache_iTree}->{$chr}->fetch($min,$max)};
+  return undef unless(@data);
+  my @out;
+  for my $overlap(@data){
+    for my $item(@{$overlap}) {
+      unless(ref $item) { # turn string into object
+        my $VAR1;
+        eval $item;
+        $VAR1->{_cdnaseq} = $self->_getTranscriptSeq($VAR1);
+        $item = $VAR1;
+      }
+      push @out, $item;
+    }
   }
-  return $out;
+  @out = sort _sort_itree @out;
+  return \@out;
 }
 
-sub _init {
-	my $self = shift;
-  my %vars = @_;
-  foreach my $k(keys(%vars)){
-    if($k eq 'cache'){
-      $self->_setCacheFile($vars{$k});
-    }
+sub _sort_itree {
+  if($a->{_genomicminpos} != $b->{_genomicminpos}) {
+    return $a->{_genomicminpos} <=> $b->{_genomicminpos};
+  }
+  if($a->{_genomicmaxpos} != $b->{_genomicmaxpos}) {
+    return $a->{_genomicmaxpos} <=> $b->{_genomicmaxpos};
   }
+  return 0;
+}
+
+sub _init {
+	my ($self, %vars) = @_;
+  $self->_setCacheFile($vars{'cache'});
+  $self->{_sorted} = $vars{'sorted'};
 }
 
 sub _setCacheFile {