Mandos

For an input chemical compound, Mandos extracts a wealth of information about its known classification, disease indications, target activity, etc., and presents that data in a consistent, highly human-readable and machine-readable form.

Each annotation is a triple of (compound, predicate, object) with additional data. For example, to describe one of the targets involved in the mechanism of action (MoA) of cocaine:

cocaine    antagonist of    voltage-gated sodium channel    〈additional data〉

The output for each query (on a set of compounds) is a CSV file with columns compound, compound ID,*predicate*, predicate ID, object, object ID, annotation ID, and source, plus columns specific to the annotation type (e.g. IC50). It can also perform structural similarity searches to extract annotations for known compounds that are highly similar to your input compounds.

The main use cases are:

  • To summarize known information about a compound and its biological activity in a consistent, computationally tractable form. For consumption by other tools.

  • To identify pharmacological features that distinguish hits from non-hits in chemical screens.

  • To cluster hit compounds in any number of pharmacological spaces. For example, a scatter plot with UMAP, with the compounds colored by a score from the screen.

  • To train and/or evaluate an algorithm that predicts any of these data types. For example, to curate a set of known molecular targets.

  • As negative, or adversarial controls, to determine whether your results are overly correlated with simple measures like pKa, molecular size, or even deposition date.

Warning

Mandos is in an alpha state, and this documentation may not be accurate.

Example usage

Mandos can be called as a Python API, or as a command-line tools. The command-line tool is called with:

mandos 〈type〉 〈compound-list.txt〉

Where type is the name of an annotation type (source), and compound-list.txt is just a line-by-line text file of compound InChI Keys. It can also be a CSV file (or .tsv, .feather, etc.) with additional columns.

For example:

mandos chembl:mechanism compounds.txt

The output is a CSV file. Excluding additional columns, the findings can be summarized as:

CHEMBL661 (alprazolam)  positive allosteric modulator  CHEMBL2093872 (GABA-A receptor; anion channel)
...

Annotation types

Currently, all annotations are accessed from one of there primary sources: ChEMBL, DrugBank, or the Human Metabolome Database (HMDB). Those from PubChem are mostly derived from other sources, such as DrugBank. The types are organized either as chembl:〈type〉, or as 〈section〉.〈source〉:〈type〉, where section approximately corresponds to the name of a section on the PubChem webpage for a PubChem compound. For example, see the PubChem entry for cocaine. One section is called Pharmacology and Biochemistry; these are grouped under the pharma section in Mandos.

See below for the full list of annotations. Documentation about each of these types can be found by running mandos 〈type〉 --help (e.g. mandos chembl:go --help). The vast majority of these have various parameters and flags. For example, chembl:trials can filter by the phase of the trial, and chembl:binding can filter by the species taxonomy, minimum score, target mapping confidence, etc. You can pass these with --〈param〉 〈value〉 or --flag. All parameters have defaults, but they may not be appropriate for a given use case. More important parameters (such as taxon) are marked as such in the help.

All data fetched from ChEMBL and PubChem are cached under ~/.mandos. This means that if you modify the parameters for a query and re-run, the results should be returned quickly. For example, if you run mandos chembl:binding compounds.txt --taxa human, then running mandos chembl:binding compounds.txt --taxa @all later will be fast.

Below is the full list of annotation types that are available at the command-line. More can be found in the Python API; these are generally too specialized to be commonly used. Some types also warrant dedicated documentation, which can be found in other pages on this site.

Hint

The names of commands are always in the form source : type, with sub-categories of the source or type joined with a .. For example, in drug.dea:schedule, the source is drug.dea and the type is schedule. In chembl:go.process, the source is chembl and the type is go.process. You can always run mandos --help to see the command names.

search

description

chembl:mechanism

ChEMBL molecular mechanism annotations

chembl:binding

ChEMBL binding activity annotations

chembl:functional

ChEMBL functional activity annotations

chembl:admet

ChEMBL ADMET activity annotations

chembl:atc

ATC codes as listed by ChEMBL

chembl:trials

ChEMBL indication annotations as MESH IDs

chembl:go.function

GO Function terms of ChEMBL targets

chembl:go.process

GO Process terms of ChEMBL targets

chembl:go.component

GO Component terms of ChEMBL targets

summary.ncit:link

Compounds linked from the NCIt summary

chem.pubchem:computed

Computed chemical properties on PubChem

drug.livertox:class

LiverTox drug classes

drug.dea:class

DEA drug classes

drug.dea:schedule

DEA schedules

drug.hsdb:uses

Uses from the HSDB

drug.trials:mesh

MeSH codes from clinicaltrials.gov

pharma.mesh:mesh

MeSH codes listed on PubChem

pharma.atc:atc

ATC codes listed on PubChem

pharma.drugbank:link

Linked compounds in the DrugBank summary

pharma.hsdb:link

Linked compounds in the HSDB summary

pharma.drugbank:moa

Linked compounds in the DrugBank MoA summary

pharma.hsdb:moa

Linked compounds in the HSDB MoA summary

use.cpdat:category

Categories from the Chemical and Product Categories

safety.echa:ghs

GHS hazard codes from the European Chemicals Agency

tox.chemidplus:acute

Names of acute effects from ChemIDplus

tox.chemidplus:ld50

Empirical LD50 by organism from ChemIDplus

disease.ctd:mesh

Associated diseases and disorders from the CTD

lit.pubchem:mesh

MeSH codes from associated PubMed articles

lit.pubchem:chemical

Names of compounds co-occurring in the literature

lit.pubchem:gene

Names of genes co-occurring in the literature

lit.pubchem:disease

Names of diseases co-occurring in the literature

inter.dgidb:gene

Drug–gene interactions from the DGIDB

inter.ctd:gene

Chemical–gene interactions from the CTD

inter.drugbank:target

Protein target names from DrugBank

inter.drugbank:fn

Functions of protein targets from DrugBank

inter.drugbank:pk

Transporters, carriers, and enzymes from DrugBank

inter.drugbank:pk-fn

Functions of PK-related proteins from DrugBank

inter.drugbank:ddi

Drug–drug interactions from DrugBank

inter.pubchem:react

Names of pathways from reactions on PubChem

assay.pubchem:activity

Targets from bioAssay activity on PubChem

hmdb:tissue

Tissues listed on HMDB

hmdb:computed

Computed chemical properties from HMDB

drugbank:dosage

Dosage information from DrugBank

drugbank:metabolite

Names of known metabolites from DrugBank

drugbank:admet

Properties predicted from admetSAR via DrugBank

meta:random

Random values 1…n (with replacement)