A New Machine Learning-Based Framework for Mapping Uncertainty Analysis in RNA-Seq Read Alignment and Gene Expression Estimation

Frontiers in Genetics
Adam McDermaidQin Ma


One of the main benefits of using modern RNA-Sequencing (RNA-Seq) technology is the more accurate gene expression estimations compared with previous generations of expression data, such as the microarray. However, numerous issues can result in the possibility that an RNA-Seq read can be mapped to multiple locations on the reference genome with the same alignment scores, which occurs in plant, animal, and metagenome samples. Such a read is so-called a multiple-mapping read (MMR). The impact of these MMRs is reflected in gene expression estimation and all downstream analyses, including differential gene expression, functional enrichment, etc. Current analysis pipelines lack the tools to effectively test the reliability of gene expression estimations, thus are incapable of ensuring the validity of all downstream analyses. Our investigation into 95 RNA-Seq datasets from seven plant and animal species (totaling 1,951 GB) indicates an average of roughly 22% of all reads are MMRs. Here we present a machine learning-based tool called GeneQC (Gene expression Quality Control), which can accurately estimate the reliability of each gene's expression level derived from an RNA-Seq dataset. The underlying algorithm is designed based on extr...Continue Reading


Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
May 3, 2008·Science·Ugrappa NagalakshmiMichael Snyder
Nov 19, 2008·Nature Reviews. Genetics·Zhong WangMichael Snyder
Feb 24, 2009·Proceedings of the National Academy of Sciences of the United States of America·D R Yoder-HimesR Sorek
Mar 18, 2009·Bioinformatics·Cole TrapnellSteven L Salzberg
May 26, 2009·Nucleic Acids Research·Jing ChenAnil G Jegga
Nov 3, 2009·Nature Biotechnology·Byung-Kwan ChoBernhard Ø Palsson
Nov 20, 2009·Nucleic Acids Research·Marco AlbrechtThomas Rudel
Dec 22, 2009·Bioinformatics·Bo LiColin N Dewey
Jan 16, 2010·Nature·Jeremy SchmutzScott A Jackson
Aug 31, 2010·Nucleic Acids Research·Kai WangJinze Liu
Dec 24, 2010·Genome Biology·Alicia OshlackMatthew D Young
Dec 31, 2010·Nature Reviews. Genetics·Fatih Ozsolak, Patrice M Milos
May 17, 2011·Nature Biotechnology·Manfred G GrabherrAviv Regev
May 31, 2011·Nature Methods·Manuel GarberCole Trapnell
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Dec 12, 2012·Nature Biotechnology·Cole TrapnellLior Pachter
Mar 30, 2013·Genome Biology·Nicolas PhilippeEric Rivals
Apr 11, 2013·Nucleic Acids Research·Jie WuChaolin Zhang
Nov 15, 2013·Nucleic Acids Research·Henrik NordbergInna Dubchak
Jul 19, 2014·Science·International Wheat Genome Sequencing Consortium (IWGSC)
Sep 28, 2014·Bioinformatics·Simon AndersWolfgang Huber
Jan 22, 2015·Nucleic Acids Research·Matthew E RitchieGordon K Smyth
Feb 19, 2015·Nature Biotechnology·Mihaela PerteaSteven L Salzberg
Feb 28, 2015·Genome Biology·Zheng ChangXiuzhen Huang
Mar 10, 2015·Nature Methods·Daehwan KimSteven L Salzberg
May 1, 2015·BMC Bioinformatics·Thomas BonfertCaroline C Friedel
Sep 4, 2015·BMC Bioinformatics·Hamid YounesySteven Jm Jones
Nov 1, 2015·Bioinformatics·André KahlesGunnar Rätsch
Nov 29, 2015·Nucleic Acids Research·NCBI Resource Coordinators
Mar 24, 2016·Methods in Molecular Biology·Thomas D WuMatthew J Brauer
Apr 5, 2016·Nature Biotechnology·Nicolas L BrayLior Pachter
Aug 26, 2016·Nature Protocols·Mihaela PerteaSteven L Salzberg
Dec 13, 2016·Nature Methods·Giacomo BaruzzoGregory R Grant
Mar 8, 2017·Scientific Reports·Xin ChenYing Xu
Jun 6, 2017·Nature Methods·Harold PimentelLior Pachter


Nov 19, 2019·Frontiers in Microbiology·Qin MaSenthil Subramanian
Jul 26, 2019·Nature Reviews. Genetics·Rory StarkJames Hadfield
Jul 9, 2020·Computational and Structural Biotechnology Journal·Gabrielle Deschamps-FrancoeurMichelle S Scott

Related Concepts

Ehlers-Danlos Syndrome
Gene Expression
Research Personnel
Measles-mumps-rubella Vaccination
Learning and Learning Problems

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Synthetic Genetic Array Analysis

Synthetic genetic arrays allow the systematic examination of genetic interactions. Here is the latest research focusing on synthetic genetic arrays and their analyses.

Congenital Hyperinsulinism

Congenital hyperinsulinism is caused by genetic mutations resulting in excess insulin secretion from beta cells of the pancreas. Here is the latest research.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Epigenetic Memory

Epigenetic memory refers to the heritable genetic changes that are not explained by the DNA sequence. Find the latest research on epigenetic memory here.

Cell Atlas of the Human Eye

Constructing a cell atlas of the human eye will require transcriptomic and histologic analysis over the lifespan. This understanding will aid in the study of development and disease. Find the latest research pertaining to the Cell Atlas of the Human Eye here.

Femoral Neoplasms

Femoral Neoplasms are bone tumors that arise in the femur. Discover the latest research on femoral neoplasms here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.