Output Results of CLIME (Clustering by Inferred Models of Evolution)

Output results of CLIME (CLustering by Inferred Models of Evolution)

Dataset: Num of genes in input gene set: 3 Total number of genes: 20834 Prediction LLR threshold: 0

The CLIME PDF output two sections: 1) Overview of Evolutionarily Conserved Modules (ECMs)

Top panel shows the predefined species tree.

Bottom panel shows the partition of input genes into Evolutionary Conserved Modules (ECMs), ordered by ECM strength (shown at right), and separated by horizontal lines.

Each row show one gene, where the phylogenetic profile indicates presence (blue) or absence (gray) of homologs in each species (column).

Gene symbols are shown at left. Gray color indicates that the gene is a paralog to a higher scoring gene within the same ECM (based on BLASTP E < 1e-3).

2) Details of each ECM and its expansion ECM+

Top panel shows the inferred evolutionary history on the predefined species tree. Branch color shows the gain event (blue) and loss events (red color, with brighter color indicating higher confidence in loss). Branches before the gain or after a loss are shown in gray.

Bottom panel shows the input genes that are within the ECM (blue/white rows) as well as all genes in the expanded ECM+ (green/gray rows). The ECM+ includes genes likely to have arisen under the inferred model of evolution relative to a background model, and scored using a log likelihood ratio (LLR).

PG indicates "paralog group" and are labeled alphabetically (i.e., A, B). The first gene within each paralog group is shown in black color. All other genes sharing sequence similarity (BLAST E < 1e-3) are assigned to the same PG label and displayed in gray. ECM 1 Protein ETFDH ETFA ETFB Overview ofEvolutionarilyConservedModules(ECMs)

Prokaryotes Prokaryotes Last CommonAncestor E.cuniculi E.cuniculi E.histolytica E.histolytica E.dispar E.dispar G.lamblia G.lamblia T.vaginalis T.vaginalis T.brucei T.brucei T.cruzi T.cruzi L.infantum L.infantum L.major L.major L.braziliensis L.braziliensis T.gondii T.gondii Protists C.hominis C.hominis C.parvum C.parvum B.bovis B.bovis T.annulata T.annulata T.parva T.parva P.knowlesi P.knowlesi P.vivax P.vivax P.falciparum P.falciparum P.chabaudi P.chabaudi P.berghei P.berghei P.yoelii P.yoelii P.tetraurelia P.tetraurelia T.thermophila T.thermophila P.infestans P.infestans T.pseudonana T.pseudonana P.tricornutum P.tricornutum C.merolae C.merolae N.gruberi N.gruberi O.lucimarinus O.lucimarinus O.tauri O.tauri C.reinhardtii C.reinhardtii V.carteri V.carteri P.patens P.patens

S.moellendorffii Plants S.moellendorffii S.bicolor S.bicolor Z.mays Z.mays O.sativa O.sativa B.distachyon B.distachyon A.lyrata A.lyrata A.thaliana A.thaliana L.japonicus L.japonicus M.truncatula M.truncatula V.vinifera V.vinifera P.trichocarpa P.trichocarpa R.communis R.communis T.trahens T.trahens D.discoideum D.discoideum A.macrogynus A.macrogynus S.punctatus S.punctatus M.globosa M.globosa U.maydis U.maydis C.neoformans C.neoformans P.chrysosporium P.chrysosporium S.commune S.commune C.cinerea C.cinerea L.bicolor L.bicolor S.pombe S.pombe B.fuckeliana B.fuckeliana S.sclerotiorum S.sclerotiorum F.graminearum F.graminearum M.grisea M.grisea N.crassa N.crassa P.anserina P.anserina P.chrysogenum P.chrysogenum A.clavatus A.clavatus A.fumigatus A.fumigatus N.fischeri N.fischeri A.flavus A.flavus A.oryzae A.oryzae A.niger A.niger A.nidulans Fungi A.nidulans U.reesii U.reesii C.immitis C.immitis C.posadasii C.posadasii P.nodorum P.nodorum T.melanosporum T.melanosporum Y.lipolytica Y.lipolytica P.pastoris P.pastoris C.lusitaniae C.lusitaniae D.hansenii D.hansenii M.guilliermondii M.guilliermondii S.stipitis S.stipitis L.elongisporus L.elongisporus C.tropicalis C.tropicalis C.albicans C.albicans C.dubliniensis C.dubliniensis K.lactis K.lactis A.gossypii A.gossypii K.waltii K.waltii L.thermotolerans L.thermotolerans Z.rouxii Z.rouxii V.polyspora V.polyspora C.glabrata C.glabrata S.bayanus S.bayanus S.mikatae S.mikatae S.cerevisiae S.cerevisiae S.paradoxus S.paradoxus S.arctica S.arctica C.owczarzaki C.owczarzaki M.brevicollis M.brevicollis S.rosetta S.rosetta S.mansoni S.mansoni B.malayi B.malayi C.briggsae C.briggsae C.elegans C.elegans D.pulex D.pulex A.pisum A.pisum P.humanus P.humanus A.mellifera A.mellifera N.vitripennis N.vitripennis B.mori B.mori T.castaneum T.castaneum D.melanogaster D.melanogaster D.pseudoobscura D.pseudoobscura A.gambiae A.gambiae A.aegypti A.aegypti

C.quinquefasciatus Metazoa C.quinquefasciatus B.floridae B.floridae T.adhaerens T.adhaerens S.purpuratus S.purpuratus H.magnipapillata H.magnipapillata N.vectensis N.vectensis C.intestinalis C.intestinalis D.rerio D.rerio O.latipes O.latipes F.rubripes F.rubripes T.nigroviridis T.nigroviridis X.tropicalis X.tropicalis G.gallus G.gallus M.gallopavo M.gallopavo O.anatinus O.anatinus M.domestica M.domestica S.scrofa S.scrofa M.musculus M.musculus C.familiaris C.familiaris B.taurus B.taurus H.sapiens H.sapiens Strength 12.3 PG A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A Protein CYP11B2 CYP4A11 CYP11A1 CYP27B1 CYP4A22 CYP17A1 CYP27C1 CYP11B1 CYP24A1 CYP21A2 CYP26A1 CYP26B1 CYP46A1 CYP3A43 CYP4F11 CYP4F22 CYP4F12 CYP2A6 CYP3A4 CYP4B1 CYP2U1 CYP2D6 CYP3A7 CYP2C8 CYP3A5 CYP2B6 CYP2S1 CYP4X1 CYP4V2 CYP4F8 CYP4F3 CYP4F2 ETFDH ETFA ETFB 1: Glutaric acidemia|| Num ofECMGenes:3.Predicted100.Strength:12.3 ECM 1,Geneset"Glutaricacidemia",Page1

Prokaryotes Prokaryotes Last CommonAncestor E.cuniculi E.cuniculi E.histolytica E.histolytica E.dispar E.dispar G.lamblia G.lamblia T.vaginalis T.vaginalis T.brucei T.brucei T.cruzi T.cruzi L.infantum L.infantum L.major L.major L.braziliensis L.braziliensis 2: Adrenal hyperplasia|| T.gondii T.gondii Protists C.hominis C.hominis C.parvum C.parvum B.bovis B.bovis T.annulata T.annulata T.parva T.parva P.knowlesi P.knowlesi P.vivax P.vivax P.falciparum P.falciparum P.chabaudi P.chabaudi P.berghei P.berghei P.yoelii P.yoelii P.tetraurelia P.tetraurelia T.thermophila T.thermophila 3: Ichthyosis P.infestans P.infestans T.pseudonana T.pseudonana P.tricornutum P.tricornutum C.merolae C.merolae N.gruberi N.gruberi O.lucimarinus O.lucimarinus O.tauri O.tauri C.reinhardtii C.reinhardtii V.carteri V.carteri P.patens P.patens

K.lactis K.lactis PRESENCE A.gossypii A.gossypii K.waltii K.waltii

L.thermotolerans L.thermotolerans GAIN Z.rouxii Z.rouxii V.polyspora V.polyspora C.glabrata C.glabrata S.bayanus S.bayanus S.mikatae S.mikatae S.cerevisiae S.cerevisiae S.paradoxus S.paradoxus S.arctica S.arctica C.owczarzaki C.owczarzaki M.brevicollis M.brevicollis S.rosetta S.rosetta

S.mansoni S.mansoni ABSENCE B.malayi B.malayi

C.briggsae C.briggsae LOSS C.elegans C.elegans D.pulex D.pulex A.pisum A.pisum P.humanus P.humanus A.mellifera A.mellifera N.vitripennis N.vitripennis B.mori B.mori T.castaneum T.castaneum D.melanogaster D.melanogaster D.pseudoobscura D.pseudoobscura A.gambiae A.gambiae A.aegypti A.aegypti

C.quinquefasciatus Metazoa C.quinquefasciatus B.floridae B.floridae T.adhaerens

T.adhaerens 0 Log-likelihood RatioScale S.purpuratus S.purpuratus H.magnipapillata H.magnipapillata 10 N.vectensis N.vectensis C.intestinalis C.intestinalis

D.rerio D.rerio 20 O.latipes O.latipes

F.rubripes F.rubripes 30 T.nigroviridis T.nigroviridis X.tropicalis X.tropicalis 40 G.gallus G.gallus M.gallopavo M.gallopavo

O.anatinus O.anatinus 50 M.domestica M.domestica S.scrofa S.scrofa 60 M.musculus M.musculus C.familiaris C.familiaris B.taurus B.taurus H.sapiens H.sapiens LLR 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.6 33.7 Notes 3 2 2 1 1 1 PG D D A A A D A A B B A A A A A A A A A A C B B A A A A A A A Protein CYP21A1P CYP21A1P CYP39A1 CYP20A1 CYP2A13 CYP2C19 CYP2C18 CYP51A1 CYP27A1 CYP19A1 D2HGDH CYP2W1 CYB5RL TBXAS1 CYP7B1 CYP7A1 CYP2A7 CYP2R1 CYP2C9 CYP1A1 CYP2F1 CYP4Z1 CYP2J2 ACADM ACOXL ACADL ACOX3 CRYL1 GSTT1 HIBCH PTGIS AGPS LDHD CYC1 CAT 1: Acyl-CoA dehydrogenase || Num ofECMGenes:3.Predicted100.Strength:12.3 ECM 1,Geneset"Glutaricacidemia",Page2

2: Hypertension || B.bovis T.annulata T.annulata T.parva T.parva P.knowlesi P.knowlesi P.vivax P.vivax P.falciparum P.falciparum P.chabaudi P.chabaudi P.berghei P.berghei P.yoelii P.yoelii P.tetraurelia P.tetraurelia T.thermophila T.thermophila P.infestans P.infestans 3: Spastic paraplegia|| T.pseudonana T.pseudonana P.tricornutum P.tricornutum C.merolae C.merolae N.gruberi N.gruberi O.lucimarinus O.lucimarinus O.tauri O.tauri C.reinhardtii C.reinhardtii V.carteri V.carteri P.patens P.patens

S.moellendorffii Plants S.moellendorffii S.bicolor S.bicolor Z.mays Z.mays O.sativa O.sativa 4: Bileacid synthesisdefect || B.distachyon B.distachyon A.lyrata A.lyrata A.thaliana A.thaliana L.japonicus L.japonicus M.truncatula M.truncatula V.vinifera V.vinifera P.trichocarpa P.trichocarpa R.communis R.communis T.trahens T.trahens D.discoideum D.discoideum A.macrogynus A.macrogynus S.punctatus S.punctatus M.globosa M.globosa U.maydis U.maydis C.neoformans C.neoformans P.chrysosporium P.chrysosporium

5: Rhizomelic chondrodysplasia punctata || S.commune S.commune C.cinerea C.cinerea L.bicolor L.bicolor S.pombe S.pombe B.fuckeliana B.fuckeliana S.sclerotiorum S.sclerotiorum F.graminearum F.graminearum M.grisea M.grisea N.crassa N.crassa P.anserina P.anserina P.chrysogenum P.chrysogenum A.clavatus A.clavatus A.fumigatus A.fumigatus N.fischeri N.fischeri A.flavus A.flavus A.oryzae A.oryzae A.niger A.niger A.nidulans Fungi A.nidulans U.reesii U.reesii C.immitis C.immitis C.posadasii C.posadasii P.nodorum P.nodorum T.melanosporum T.melanosporum 6: D-2-hydroxyglutaric aciduria Y.lipolytica Y.lipolytica P.pastoris P.pastoris C.lusitaniae C.lusitaniae D.hansenii D.hansenii M.guilliermondii M.guilliermondii S.stipitis S.stipitis L.elongisporus L.elongisporus C.tropicalis C.tropicalis C.albicans C.albicans C.dubliniensis C.dubliniensis

K.lactis K.lactis PRESENCE A.gossypii A.gossypii K.waltii K.waltii

S.mansoni S.mansoni ABSENCE B.malayi B.malayi

C.quinquefasciatus Metazoa C.quinquefasciatus B.floridae B.floridae T.adhaerens

T.adhaerens 0 Log-likelihood RatioScale S.purpuratus S.purpuratus H.magnipapillata H.magnipapillata 10 N.vectensis N.vectensis C.intestinalis C.intestinalis

D.rerio D.rerio 20 O.latipes O.latipes

F.rubripes F.rubripes 30 T.nigroviridis T.nigroviridis X.tropicalis X.tropicalis 40 G.gallus G.gallus M.gallopavo M.gallopavo

O.anatinus O.anatinus 50 M.domestica M.domestica S.scrofa S.scrofa 60 M.musculus M.musculus C.familiaris C.familiaris B.taurus B.taurus H.sapiens H.sapiens LLR 18.8 18.9 18.9 18.9 18.9 18.9 18.9 18.9 19.0 19.7 20.0 20.2 21.2 21.2 21.2 21.2 21.2 21.2 21.2 21.2 21.2 21.2 21.2 22.0 22.5 24.0 25.4 30.5 31.1 33.6 33.6 33.6 33.6 33.6 33.6 Notes 6 5 3 /4 2 1 PG C J J J J B F I I H H G G A A A B F F B B B E E A LOC100130673 Protein SLC22A13 CACNA1F CYP26C1 SLC22A4 ACADSB PRODH2 BOLA2B CYP8B1 CYP1B1 CYP2E1 MSMO1 ACADS ACOX2 ACOX1 ACAD9 SVOPL BOLA2 CNDP1 BCAT2 BCAT1 SC5DL JMJD4 MSRA HADH FMO4 FMO2 FMO5 FMO1 CDYL PDK3 PDK1 CS 1: Acyl-CoAdehydrogenase || Num ofECMGenes:3.Predicted100.Strength:12.3 ECM 1,Geneset"Glutaricacidemia",Page3

2: Glaucoma|| B.bovis T.annulata T.annulata T.parva T.parva P.knowlesi P.knowlesi P.vivax P.vivax P.falciparum P.falciparum P.chabaudi P.chabaudi P.berghei P.berghei P.yoelii P.yoelii P.tetraurelia P.tetraurelia

3: Petersanomaly || T.thermophila T.thermophila P.infestans P.infestans T.pseudonana T.pseudonana P.tricornutum P.tricornutum C.merolae C.merolae N.gruberi N.gruberi O.lucimarinus O.lucimarinus O.tauri O.tauri C.reinhardtii C.reinhardtii V.carteri V.carteri P.patens P.patens

S.moellendorffii Plants S.moellendorffii

4: Cone-roddystrophy || S.bicolor S.bicolor Z.mays Z.mays O.sativa O.sativa B.distachyon B.distachyon A.lyrata A.lyrata A.thaliana A.thaliana L.japonicus L.japonicus M.truncatula M.truncatula V.vinifera V.vinifera P.trichocarpa P.trichocarpa R.communis R.communis T.trahens T.trahens D.discoideum D.discoideum A.macrogynus A.macrogynus

5: Nightblindness || S.punctatus S.punctatus M.globosa M.globosa U.maydis U.maydis C.neoformans C.neoformans P.chrysosporium P.chrysosporium S.commune S.commune C.cinerea C.cinerea L.bicolor L.bicolor S.pombe S.pombe B.fuckeliana B.fuckeliana S.sclerotiorum S.sclerotiorum F.graminearum F.graminearum

6: Hyperinsulinemic hypoglycemia M.grisea M.grisea N.crassa N.crassa P.anserina P.anserina P.chrysogenum P.chrysogenum A.clavatus A.clavatus A.fumigatus A.fumigatus N.fischeri N.fischeri A.flavus A.flavus A.oryzae A.oryzae A.niger A.niger A.nidulans Fungi A.nidulans U.reesii U.reesii C.immitis C.immitis C.posadasii C.posadasii P.nodorum P.nodorum T.melanosporum T.melanosporum Y.lipolytica Y.lipolytica P.pastoris P.pastoris C.lusitaniae C.lusitaniae D.hansenii D.hansenii M.guilliermondii M.guilliermondii S.stipitis S.stipitis L.elongisporus L.elongisporus C.tropicalis C.tropicalis C.albicans C.albicans C.dubliniensis C.dubliniensis

K.lactis K.lactis PRESENCE A.gossypii A.gossypii K.waltii K.waltii

S.mansoni S.mansoni ABSENCE B.malayi B.malayi

C.quinquefasciatus Metazoa C.quinquefasciatus B.floridae B.floridae T.adhaerens

T.adhaerens 0 Log-likelihood RatioScale S.purpuratus S.purpuratus H.magnipapillata H.magnipapillata 10 N.vectensis N.vectensis C.intestinalis C.intestinalis

D.rerio D.rerio 20 O.latipes O.latipes

F.rubripes F.rubripes 30 T.nigroviridis T.nigroviridis X.tropicalis X.tropicalis 40 G.gallus G.gallus M.gallopavo M.gallopavo

O.anatinus O.anatinus 50 M.domestica M.domestica S.scrofa S.scrofa 60 M.musculus M.musculus C.familiaris C.familiaris B.taurus B.taurus H.sapiens H.sapiens LLR 12.9 13.1 13.4 13.5 13.5 13.5 13.5 13.8 13.8 13.9 14.0 14.0 14.0 14.9 15.5 15.8 15.9 16.0 16.2 16.2 16.3 16.4 16.4 17.3 17.7 17.7 18.1 18.1 18.1 18.7 18.7 18.8 18.8 Notes 6 4 /5 2 /3 1