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Xiaotao JIANG (姜小濤) edited this page Jan 16, 2018 · 1 revision

aqmm

Document for AQMM (Absolute quantification of metagenome and metatranscriptome) .

The AQMM was developed to perform absolute quantification of mulitipile metagenome and it's paralell metatranscriptome. In order to use this algorithm, the experiment should be designed with both metagenome and metatranscriptome data. From initial stage, the molecular experimental data should be recorded to help on estimating the overall DNA or RNA of a unit (ml/gram) of sample. The AQMM was demonstrated to obtain better results of differential experssion genes identification in comparative metatranscriptomic studies.

clone the source code to local server .

git clone https://github.com/biofuture/aqmm.git .  

prepare the meta_data.txt which contains all the molecular experimental data .  

The meta_data.txt should .

SID SNAME   DNA_weight     DNA_volume     DNA_extr_eff   RNA_weight     RNA_volume     RNA_extr_eff   mRNA_ratio
1       AS1     24570   0.5     0.282   6135   0.5     0.075   0.03
2       AS2     27300   0.5     0.282   6355   0.5     0.075   0.03

Each line contains information of one sample .

SNAME is the name of the sample, which stored under the input directory .
DNA_weight is the weight of DNA for the extraction (ng) .
DNA_volume is the total volume of sample used for the DNA extraction .
DNA_extr_eff is the extracting efficiency for the sample, which is an emperical value for a DNA extraction KIT for a sample .
RNA_weight is the weight of RNA for the extraction .
RNA_volume is the total volume of sample used for the RNA extraction .
RNA_extr_eff is the extracting efficiency for the sample, which is an emperical value for a RNA extraction KIT for a type of sample .
mRNA ratio is the ratio of mRNA to total RNA, which is a emperical value for different environment

Notice: Before using this algorithm, users need to get the above meta data information as accurately as possible, although the algorithm show robusty to the variance to the extraction efficiency among different samples, users should keep all the condition as consistent as possible in order to get more accurate/reliable quantification and comparativety.

Running the aqmm just by one command .

By typing ./aqmm -h the help information will show here .  

perl ./aqmm -a <Input_metagenome_dir> -b <Input_metatranscriptome_dir> -m <Experimental_meta_data> -n <num_threads> -o <ouput_dir>
Author Jiang Xiao-Tao 2017-08
Email  biofuture.jiang@gmail.com

where:

   -a <Input_metagenome_dir> including all the fq files of your metagenomic samples after quality filtering
   
   -b <Input_metatranscriptome_dir> including all the paralell metatranscriptomic fq files with metagenomic samples after . remvoing the rRNA with tools like SortMeRNA.
   
   -m meta_data.txt including all the experimental extraction information and the extraction efficiency information of your sample type
   
   -o <ouput_dir> will include all the output results for the quantification, including the esimated cell numbers of metagenomic data of each sample and the estimated sequenced cell numbers your metatranscriptomic data included. With the quantification results obtained, the abundance of gene/species could be futher normalized to per cell/volume/gram etc. al.   

Example to run

There is a small demo to show how to use AQMM to generate absolute quantification of your data under the example directory.

Enter the example directory and run the following command

../dist/aqmm  -a AS_metagenome -b AS_metatranscriptome -m meta_data.txt -n 12 -o testout

After runnning, check the results

cat dna_cell_info.txt .   
SID SNAME library_size lib_cell cell_per_ml A_ratio T_ratio C_ratio G_ratio
1 AS2 50000000 8.56742513314301 3.23275242169008e+19 0.22371768 0.22220922 0.27649788 0.27757522
2 AS1 50000000 9.93418747046929 3.37319232480681e+19 0.21272236 0.21128754 0.28672574 0.28926436
cat rna_cell_info.txt .
SID SNAME library_size lib_cell cell_per_ml A_ratio T_ratio C_ratio G_ratio
1 AS2 50000000 8.56742513314301 3.23275242169008e+19 0.22371768 0.22220922 0.27649788 0.27757522
2 AS1 50000000 9.93418747046929 3.37319232480681e+19 0.21272236 0.21128754 0.28672574 0.28926436

These numbers could be used to normalize your genes/species to per cell/volume level in the end!

Compare with RQ methods

A script was developed to process the results for both AQMM and RQ methods like RPKM/TPM/edgeR to identify the differential expression genes between groups

perl normalization_RNA_sequencing.pl <RNA_Depth> <gene_length> <RNA_Table> <Oprefix>

where

RNA_Depth	is the meta_data file contains the the library size of each sample 
gene_length	is the file contains all the gene length information
RNA_Table	is the coverage matrix of each gene in different samples generated by mapping process
Oprefix	        is the output prefix for all the normalization methods for the RNA_Table 

I will show the our foaming vs nonfoaming activated sludge as the example

cat RNA_DEPTH.txt

NAME	lib.size	Group
RNA-201.gene.txt	148949591	Foaming
RNA-202.gene.txt	181507132	Foaming
RNA-203.gene.txt	135988557	Foaming
RNA-205.gene.txt	152020602	NonFoaming
RNA-206.gene.txt	155510444	Foaming
RNA-207.gene.txt	161566079	NonFoaming
RNA-208.gene.txt	148860009	NonFoaming
RNA-209.gene.txt	132982810	Foaming
RNA-210.gene.txt	137007411	NonFoaming

head -10 len_gene.txt

contig_1_1	1071
contig_1_2	552
contig_1_3	1284
contig_1_4	279
contig_1_5	699
contig_1_6	867

Supporting for time series metatranscriptomics studies

As many metatranscriptomics studies only investiagte the activity of a system without change of the DNA part, hence this is a very important application scence. To perform absolute quantification of this condition, a optional parameters were integrated into the aqmm tool. Users process this type of data could quantify the transcript in this way. Inputing the relative abundance informaition, per species quantification could be achieved.

Copyright: LG209, Environmental biotechnology laborotory HKU.