Unconfigured Ad

Collapse
X
 
  • Time
  • Show
Clear All
new posts
  • ccard28
    Member
    • Jan 2012
    • 20

    #1

    Cuffdiff results; no replicates

    Hello everyone,

    We are working with some data in lab in which we are comparing two different treatments but did not have the sample means necessary for replicates. When I run cuffdiff I only get 30 or so transcripts that are significantly DE out of the few thousand or so. The weird part is that all of these transcripts it finds significant are expressed in one sample at a fairly high level and not expressed in the other sample at all. When running DESeq I am seeing no significance in any transcripts for DE analysis. This information seems rather non-essential to be kind and I know our problem is no replicates. Telling me that a transcript that isn't even expressed in one population but highly in the other(cuffdiff) is differentially expressed is stating the very obvious.

    My thoughts on how to approach our data are as follows and I was looking for some more RNA-Seq savvy people to let me know if this is acceptable or not as we are fairly new to RNA-Seq and this is our first sample to sample comparison.

    What I proposed we do with our data is to take cufflinks FPKM values and just simple evaluate ratios, calling anything with say 2:1 ratio DE and having higher ratios (ex. 5:1; 10:1) in separate categories. We have looked at the data in this manner and tried to validate with our little bit of leftover sample on qPCR to determine if these ratios are indeed truly represented in the sample via validation.

    Could this be an acceptable alternative to cuffdiff/deseq/etc for not having replicates and those analyses offering little to no useful information? Is validation via qPCR essential or could these ratios be reported as is?

    I feel our data is still very useful exploratory data as RNA-Seq has never been done to compare these 2 sample types but the DE analysis has been lacking due to our lack or replicates.

    Thank you in advance for any input,

    -C
  • TiborNagy
    Senior Member
    • Mar 2010
    • 329

    #2
    If DESeq did not found any significant results, maybe this is the result. The problem with the pure DE ratio is it is produce a large number of false positives.

    Comment

    • sphil
      Senior Member
      • Apr 2010
      • 192

      #3
      DESeq and all other DE software like edreR... are not capable of calculating DE-Genes w/o replicates. In fact you can't (of course you can force them but...) use this kind of software for that. Your approach of calculating fold-changes between your samples is the only way to get something out of the data. Since you have no replicates, imho you have to validate everything you want to report via qPCR / qRT-PCR just to handle the huge amount of flase positives as TiborNagy said - just my two cents.

      Comment

      • Krish_143
        Member
        • Jan 2012
        • 45

        #4
        Hi ccard28,

        I also work with similar case.. No replicates but i follow

        * Tophat-Cufflinks ( FPKM values from cufflinks not cuffdiff ) or HTSeq read count and then i do analysis based on gene of interest and high log fold differences and for those we validate with qPCR.

        Its all up to U how you setup. All the current tools are better with replicates ( That produce a bit more confident results. ). No replicates means one has to validate..

        Even with the replicates better to validate up to some extent.
        Krishna

        Comment

        • ccard28
          Member
          • Jan 2012
          • 20

          #5
          Thank you everyone for all of your input. This has helped me make a decision on our data moving forward using a variant of ratio analysis with some qPCR validation.

          Does anyone have a reference handy for an RNA-Seq paper that did not use replicates and skipped computational methods such as cuffdiff/deseq but did some validation via qPCR?

          Comment

          • Krish_143
            Member
            • Jan 2012
            • 45

            #6
            Hi ccard28,

            I tried Gfold. This seems good when no replicates.. it rank based on logfold data.

            For more details
            Look at the paper. http://www.ncbi.nlm.nih.gov/pubmed/22923299

            Source code : https://bitbucket.org/feeldead/gfold/downloads


            Have a nice time
            Krishna

            Comment

            Latest Articles

            Collapse

            • SEQadmin2
              Beyond CRISPR/Cas9: Understand, Choose, and Use the Right Genome Editing Tool
              by SEQadmin2



              CRISPR/Cas9 sparked the gene editing revolution for both research and therapeutics.1 But this system still showed severe issues that limited its applications. The most prominent were the heavy reliance on PAM sequences, delivery limitations, double-stranded breaks that prompt unintended edits and cell death, and editing inefficiency (both in targeting and in knock-in reliability).

              Despite this, “CRISPR helped turn genome editing from a specialized technique into
              ...
              07-31-2026, 11:01 AM
            • SEQadmin2
              Proteomic Platforms: How to Choose the Right Analytical Strategy to Improve Detection and Clinical Applications
              by SEQadmin2


              Proteomics platforms are evolving rapidly, with advances in mass spectrometry and affinity-based approaches expanding what researchers can detect and at what scale. As the field moves toward deeper proteome coverage and clinical applications, scientists face an increasingly complex landscape of tools. This article will explore how researchers are navigating these choices to find the right platform for their work.

              The systematic characterization of the human proteome has
              ...
              07-20-2026, 11:48 AM
            • SEQadmin2
              Advanced Sequencing Platforms Tackle Neuroscience’s Toughest Genomics Problems
              by SEQadmin2



              Genomics studies in neuroscience face a special challenge due to the brain’s complexity and scarcity of samples. Mapping changes in cell type and state using conventional next-generation sequencing methods remains challenging. Advances in technologies like single-cell sequencing, spatial transcriptomics, and long-read sequencing have opened the door to deeper studies of the brain and diseases like Alzheimer’s, amyotrophic lateral sclerosis (ALS), and schizophrenia.
              ...
              07-09-2026, 11:10 AM

            ad_right_rmr

            Collapse

            News

            Collapse

            Topics Statistics Last Post
            Started by SEQadmin2, Today, 07:41 AM
            0 responses
            9 views
            0 reactions
            Last Post SEQadmin2  
            Started by SEQadmin2, 08-03-2026, 10:13 AM
            0 responses
            25 views
            0 reactions
            Last Post SEQadmin2  
            Started by SEQadmin2, 07-31-2026, 02:55 AM
            0 responses
            38 views
            0 reactions
            Last Post SEQadmin2  
            Started by SEQadmin2, 07-24-2026, 12:17 PM
            0 responses
            25 views
            0 reactions
            Last Post SEQadmin2  
            Working...