CancerDR: Cancer Drug Resistance Database

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Guide To CancerDR



This page help the user to understand the CancerDR and how to use it effectively. Here user can get the details of all the procedures present in the different modules in a step-wise manner. User can directly go to the particular section by clicking the respective menu present in the main table. CancerDR modules require Java enabled, so please make sure that Java is enabled in your browser. For more help please refer the CancerDR manual.



SEARCHBROWSEALIGNMENT/MUTATIONTARGET STRUCTUREMAP/ALIGNMENTCLUSTERS/GROUPSDOWNLOADSFAQs
Drug Targets

Cell Lines

Drugs

Structure

Major Fields

Drug Targets

Cell Lines

Drugs

Total Align

Custom Align

Mutants

Structure Alignment

Tertiary

Secondary

Compare

User Sequence

Short Reads

Contigs

Sequences

Targets

Cell Lines

Drugs

Sequences

Alignments

Structures

Experimental Structures

Frequently Asked Questions
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SEARCH


DRUG TARGETS
Target search option allows the user to obtain detailed information about a drug target including the number of cell lines having mutated or normal drug target, protein change, cDNA change, codon change and the predicted structure of the target. The links allow user to get relevant information of drug target like protein interactions, pathway interactions and gene ontologies.

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CELL LINES
Cell line search can be done to get the tissue type to which the cell line belongs. The other column tells about the number of drugs those have been tried against that cell line.

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DRUGS
Drug search enables the user to find the structure of the drug molecule along with other molecular details. User can also search the targets of drugs and number of targets.

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STRUCTURE
Here user can search the CancerDR drugs on the basis of similarity. They can use SDF, MOL or SMILE format for their search. In addition to this, user can also draw the molecules.

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BROWSE


MAJOR FIELDS
Here user can browse the CancerDR data on the basis of two major categories. First, tissue type of cell lines used in pharmacological drug profiling. Second, molecular therapeutic targets of the anticancer drugs.

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DRUG TARGETS
Drug target browsing facilitates the user to get the comprehensive information of drug targets such as links for mutations, protein-protein interactions, pathway interactions, gene ontologies, genome browser, phylogenetic tree, chromosomal position and number of cell lines with mutated drug targets.

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CELL LINES
This browsing option enables the user to look at the number of drugs and their targets along with the information regarding the histology of the cell lines.

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DRUGS
With this option, the user can look at different descriptors of drugs like pI, Volume, Hydrogen Bond Acceptor, Hydrogen Bond Donor, Structure link, molecular target, along with other chemical properties and structures of drugs.

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ALIGNMENT/MUTATION


TOTAL ALIGN
Here user can do the multiple sequence alignment of drug targets. This is divided into two parts first, alignment of mutated sequences with wild type sequence of particular target. Second, alignment of natural variant sequences of targets available in Uniprot. Jalview is also integrated in this module to show the alignment in a better way to understand the sequence variation.

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CUSTOM ALIGN
Custom align module gives an advantage to the user to choose the mutated sequences of a particular target for multiple sequence alignment. Here user can correlate the mutated sequences with the IC50 values.

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MUTANTS
Here user can find out the how many mutations are present in particular drug targets. Mutations are available at three levels viz. cDNA, codon and protein.


STRUCTURE ALIGNMENT
This powerful module enables the user to align the tertiary structures of two or more mutants of a particular drug target to see the structural changes in respective mutants. Variants of drug targets can also be aligned here. Sequence alignment on the basis of structural alignment can also be generated over here.

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TARGET STRUCTURE


TERTIARY
Here user can view the tertiary structure of drug targets and their mutants in Jmol. In each mutant, mutated position is depicted in green color to locate the mutation region. PDB file of each structure can also be downloaded from here.

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SECONDARY
It is very important to know that which residue is present in which secondary state e.g. helix, beta sheet or turn. To keep this in mind, we obtained the secondary state of all the drug targets, mutants and natural variants by using DSSP.

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COMPARE
Compare module is built to compare the structure of two mutants of a particular drug target. Users can also compare their own structures with the any structure present in CancerDR.


USER SEQUENCE
This module is designed to predict the structure of user sequence against the targets available in CancerDR. User has to either paste the query sequence in FASTA format or upload the corresponding file containing query sequence and select any one of the targets against which structure has to be built.

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MAP/ALIGNMENT


Short Reads
This module will be used for the alignment of short reads, produced after the Next Generation Sequencing (NGS) of Transcriptome or Exome. Both types of sequencing reads i.e Paired end and single end sequencing reads can be submitted to this module.
Sequencing reads will be aligned to the Cancer target genes and visualized for any variation. Alignment visualization will clearly indicate the mutations in the sequenced genes. User has to provide the files (.fastq format) generated after the sequencing (Please see the example files). This module use BWA to generate alignment files (i.e. aln.sam file) and Tablet for visualization of the alignment files. It is necessary to provide forward and reversed read files both at a time if a user wants to use paired end data for the alignment. A single file is enough in case of single end sequencing.
Please have a look at the help pictures.

Help Pictures
Form submission

Result Page

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Contigs
In this module user can submit contigs (Genomic or transcriptomic) for the alignment of genes (extracted from those contigs) with Cancer targets. This module works in two steps. In the first step, genes have been predicted from the contigs with Augustus software. After that the predicted genes (nucleotide and proteins sequences both) will be searched for similarity with Cancer targets by BLAST. At the result page, user can analyze the Predicted genes and their alignment with cancer targets.
Please have a look at the help pictures.

Help Pictures
Form submission

Result Page


Sequences
This module will be used for the BLAST alignment of genes or protein sequences to cancer targets. User can paste the sequences or provide a file of genes to be compared. User can compare a gene or Protein sequence with cancer targets by choosing an E value of BLAST alignment. This module provides the option of different types of BLAST programs.

Help Pictures
Form submission

Result Page

CLUSTERS/GROUPS


TARGETS
To see the distance of different mutated sequences of a selected target as an alignment tree, user can select a drug target from the given list. The Alignment-tree diagram will be displayed creating the tree of all possible mutated protein sequences for that selected drug target.

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Cell Lines
With this option user can cluster cell lines against which the drug has been screened. In the same way as in drug clustering here user can group cell lines, which has been screened against that particular drug. The group of cell lines may have very low or very high IC-50 as selected.

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DRUGS
This interface presents the clustering of drugs, which have been screened against any cell line. For better analysis we have given selection options for clustering of all cell lines, clustering of cell lines based on tissue of origin and clustering of cell lines for which target is mutated. The figures in columns, from second to nine, show the number of drugs, which have IC-50 in the range given in header. The ranges are given in micro molar (uM) and increasing almost logarithmically from 0.00 to 390 uM. By selecting any figures in any column say 0.001-0.005 uM in cell line row user can get group of drugs having IC-50 value lying in this range only. Lower IC-50 value groups of drugs may be preferred and drug groups having higher IC-50 value may be less preferred as they have better drug options for that particular cell line.

DOWNLOADS


SEQUENCES
This module gives the facility to download the sequence of the drug targets along with their mutants or variant sequences in the FASTA format. User can either select a particular target and its mutants/variants or all the targets and their mutants/variants. Further, rsnyc facility is given to download all the sequence data, so that user can update data.

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ALIGNMENTS
This module gives the facility to download the multiple sequence alignments of the drug targets along with their mutants or variant in the CLUSTALW format. User can either select a particular target and its mutants/variants or all the targets and their mutants/variants. Further, rsnyc facility is given to download all the alignment data, so that user can have updated data.

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STRUCTURES
This module gives the facility to download the predicted structures of the drug targets along with their mutants or variant sequences in the PDB format. User can either select a particular target and its mutants/variants or all the targets and their mutants/variants. Further, rsnyc facility is given to download all the structure data, so that user can have updated data.

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EXPERIMENTAL STRUCTURES
This module gives the facility to download the experimental structures of the drug targets available in the PDB in the PDB format. User can either select a particular target or all the targets. Further, rsnyc facility is given to download all the structure data, so that user can have updated data.

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FREQUENTLY ASKED QUESTIONS


Q1. What is CancerDR?

Ans. CancerDR is the collection and compilation of pharmacological profiling of 148 major anticancer drugs on 952 human cell lines. CancerDR data is mainly divided into two parts, first primary data which includes drug sensitivity information (i.e. IC50 value) of each anticancer drug on various cancer cell lines, information about drugs, about cell lines and the molecular targets and the mutation data of target genes. Secondary data includes prediction of tertiary structures of the targets, sequence alignments, structural alignments, clustering of cell lines and drugs etc.

Q2. What is the source of CancerDR data?
Ans. CancerDR data is collected mainly from CCLE and COSMIC. Cancer Cell Encyclopedia (CCLE) is the huge source of pharmacological profiling data and sequencing data of 1651 genes, along with gene expression data. Catalogue of Somatic Mutation is in Cancer is also a great source of pharmacological profiling data on human cancer cell lines along with the mutation and gene expression data.

Q3. How CancerDR is different form CCLE and COSMIC?
Ans. CCLE and COSMIC are two huge resources of pharmacological drug profiling on human cancer cell lines. Not only this, these databases are also provides mutations in anticancer drug targets. Although these databases are brilliant resources, but we felt some points are not covered like effect of mutations on target structure and their relation with drug sensitivity to put some light on drug resistance issue, information about which class of drug is more effective against which cell line or tissue type and vice versa, comprehensive information about the anticancer drugs and their targets, integration of generation sequencing data. So, in order to complement these databases, we developed CancerDR to addressee the issue of drug resistance in cancer from different prospects.

Q4. How the tertiary structure of target genes and their mutants are predicted in CancerDR?
Ans. Tertiary structure of the targets and their mutants has been predicted using the HHsuite 2.0 software (open source), which performs HMM-HMM-based lightning-fast iterative sequence searching.

Q5. What are the major applications of CancerDR?
Ans.

  1. CancerDR provides information of drug sensitivity of 148 anti-cancer drugs on 952 cancer cell lines. Due to genetic alterations in cancer causing genes, drugs showing varying sensitivity on different cell lines. CancerDR provides a platform where user can easily identify which drug class is more effective for which tissue type. This data can be extrapolated to real life after further validation.

  2. CancerDR also provides information of all relevant targets of these drugs and their gene sequences. In addition, mutations in these genes have also been provided. This information is very helpful for user to understand the drug sensitivity/resistance in particular cancer.

  3. CancerDR provides structures of all wild type and their mutated drug targets. A tool has also been provided for user, where mutated and wild type target structures can be compared to understand the possible changes occurred in the mutated target.

  4. Sequencing cost is decreasing day by day, so it is now possible to sequence the whole genome of cancer patients. An important tool has been integrated in CancerDR, where user can submit their short reads and can map these reads to all cancer causing genes. By doing so, users can identify all possible mutations in their sequence of interest.

  5. By analyzing genetic alterations in drug targets and drug sensitivity profiles of drugs user can design or select the best therapeutic options for a particular cancer.


Q6. Is CancerDR data downloadable?
Ans. Yes. You can download the CancerDR data from the download link available in main menu. Download data can be downloaded in three format. First, sequence download in which user can download all the sequences together or one by one. Second, sequence alignment download and third, structure download. rsync facility is also available in each format of download.