Evidence map›Paper›PMID 26335687›Full record

SynthesisPloS one2015

Meta-Analysis of Large-Scale Toxicogenomic Data Finds Neuronal Regeneration Related Protein and Cathepsin D to Be Novel Biomarkers of Drug-Induced Toxicity.

Hyosil Kim, Ju-Hwa Kim, So Youn Kim, Deokyeon Jo, Ho Jun Park, Jihyun Kim, Sungwon Jung, Hyun Seok Kim, KiYoung Lee

Erratum issuedOpen access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.8field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 12 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Hyosil KimDepartment of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
Ju-Hwa KimSeverance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
So Youn KimDepartment of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea.
Deokyeon JoDepartment of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea.
Ho Jun ParkDepartment of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea.
Jihyun KimDepartment of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea.
Sungwon JungDepartment of Genome Medicine and Science, School of Medicine, Gachon University, Incheon, Korea.
Hyun Seok KimSeverance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
KiYoung LeeDepartment of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea.
Yonsei University · KRAjou University · KRGachon University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Undesirable toxicity is one of the main reasons for withdrawing drugs from the market or eliminating them as candidates in clinical trials. Although numerous studies have attempted to identify biomarkers capable of predicting pharmacotoxicity, few have attempted to discover robust biomarkers that are coherent across various species and experimental settings. To identify such biomarkers, we conducted meta-analyses of massive gene expression profiles for 6,567 in vivo rat samples and 453 compounds. After applying rigorous feature reduction procedures, our analyses identified 18 genes to be related with toxicity upon comparisons of untreated versus treated and innocuous versus toxic specimens of kidney, liver and heart tissue. We then independently validated these genes in human cell lines. In doing so, we found several of these genes to be coherently regulated in both in vivo rat specimens and in human cell lines. Specifically, mRNA expression of neuronal regeneration-related protein was robustly down-regulated in both liver and kidney cells, while mRNA expression of cathepsin D was commonly up-regulated in liver cells after exposure to toxic concentrations of chemical compounds. Use of these novel toxicity biomarkers may enhance the efficiency of screening for safe lead compounds in early-phase drug development prior to animal testing.

Indexed as

ToxicogeneticsAnimalsBiomarkersCathepsin DCell LineGene ExpressionHumansNerve Tissue ProteinsOncogene ProteinsBiomarkersCathepsin DNerve Tissue ProteinsNREP protein, humanOncogene Proteins

Identifiers

PMID26335687
PMCPMC4559398
OpenAlexW2122053523

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.